Next Article in Journal
Purification, Chemical Characterization and Immunomodulatory Activity of a Sulfated Polysaccharide from Marine Brown Algae Durvillaea antarctica
Next Article in Special Issue
Carotenoids Biosynthesis, Accumulation, and Applications of a Model Microalga Euglenagracilis
Previous Article in Journal
Dactylospongia elegans—A Promising Drug Source: Metabolites, Bioactivities, Biosynthesis, Synthesis, and Structural-Activity Relationship
Previous Article in Special Issue
Coelastrella terrestris for Adonixanthin Production: Physiological Characterization and Evaluation of Secondary Carotenoid Productivity
 
 
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Fucoxanthin from Algae to Human, an Extraordinary Bioresource: Insights and Advances in up and Downstream Processes

1
Ifremer, GENALG Laboratory, Unité PHYTOX, F-44000 Nantes, France
2
Unité Mixte de Recherche CNRS 7266 Littoral Environnement et Sociétés (LIENSs), Université La Rochelle, F-17042 La Rochelle, France
3
Génie des Procédés Environnement (GEPEA), Université Nantes, F-44000 Saint Nazaire, France
*
Author to whom correspondence should be addressed.
Mar. Drugs 2022, 20(4), 222; https://doi.org/10.3390/md20040222
Received: 3 March 2022 / Revised: 21 March 2022 / Accepted: 21 March 2022 / Published: 23 March 2022
(This article belongs to the Special Issue Microalgal Carotenoids)

Abstract

:
Fucoxanthin is a brown-colored pigment from algae, with great potential as a bioactive molecule due to its numerous properties. This review aims to present current knowledge on this high added-value pigment. An accurate analysis of the biological function of fucoxanthin explains its wide photon absorption capacities in golden-brown algae. The specific chemical structure of this pigment also leads to many functional activities in human health. They are outlined in this work and are supported by the latest studies in the literature. The scientific and industrial interest in fucoxanthin is correlated with great improvements in the development of algae cultures and downstream processes. The best fucoxanthin producing algae and their associated culture parameters are described. The light intensity is a major influencing factor, as it has to enable both a high biomass growth and a high fucoxanthin content. This review also insists on the most eco-friendly and innovative extraction methods and their perspective within the next years. The use of bio-based solvents, aqueous two-phase systems and the centrifugal partition chromatography are the most promising processes. The analysis of the global market and multiple applications of fucoxanthin revealed that Asian companies are major actors in the market with macroalgae. In addition, fucoxanthin from microalgae are currently produced in Israel and France, and are mostly authorized in the USA.

Graphical Abstract

1. Introduction

Fucoxanthin is the major carotenoid pigment in marine ecosystems, representing 10% of the total carotenoid production [1,2]. This yellow-orange pigment is produced by Chromista algae, a group composed of all brown and golden-brown macro and microalgae such as diatoms, haptophytes, dinophytes and brown seaweeds. Fucoxanthin masks the color of chlorophylls and gives the characteristic brown color to the Chromista. In diatoms, it was proven that fucoxanthin gives the capacity to absorb photons in a wide blue-green spectral range of visible light, which are the most available radiations in the water column [3]. Indeed, there is a lack of red light availability for chlorophylls at certain depths as only blue light can reach further to the cells. Therefore, along with the light-harvesting by chlorophylls, fucoxanthin increases the efficiency of using different light wavelength for carbon fixation.
Fucoxanthin is part of the carotenoid family named xanthophylls, whose chemical structure is distinct from the second carotenoid family, the carotenes, because they contain oxygen. This particularity along with an epoxide group and a conjugated carbonyl group confer the xanthophylls anti-oxidant properties very demanded in aquaculture, cosmetics and pharmacology [4,5,6]. Fucoxanthin, whose molecular structure was fully described in 1990. [7], is even more valuable in pharmacology as it contains an unusual allenic bond (Figure 1) that is supposed to be the origin of its anti-cancerous, anti-diabetic, anti-obesity, anti-inflammatory, anti-angiogenic, anti-malarial properties and of several protective effects [8,9,10,11,12,13]. These properties are of great interest to the food and health industry, which has increased the global demand for fucoxanthin.
The objectives of this review are multiple. As a first step, a state-of-the-art of the biological function of fucoxanthin in algae was achieved in order to provide a complete overview of this pigment, including its role in the natural environment within the golden-brown macroalgae and microalgae. The latest hypotheses on fucoxanthin synthesis are presented. Then, as a consequence of the growing interest in fucoxanthin in research and industrial fields, especially for its numerous properties (anti-cancer, anti-oxidant, anti-diabetes etc.), this review focuses on several points. The best fucoxanthin producing algae species are listed, the culture parameters of a major influence are described, and the downstream processes are categorized. Due to the high growth, ease of control and optimization in microalgal cultivation, the fucoxanthin production by microalgae has been well documented. The possibility for scaling up both production and productivity processes has already been established. In this review, research developments in production and productivity of fucoxanthin by micro and macroalgae are reported in the last three years. Since the pigments are attached to the chloroplast membrane, the state-of-the-art extraction and purification methods are also presented to find the best methods to extract the high-value substance that can be mass-produced by microalgae, with a focus on eco-friendly downstream processes. Finally, a report of the global market and applications of fucoxanthin in food, cosmetics and medicine is provided.

2. Isomers of Fucoxanthin

As other carotenoids, fucoxanthin is highly unsaturated, its molecular structure is unstable and very reactive. As a matter of fact, fucoxanthin is likely to form isomers and is sensitive to oxidation, caused by oxygen, other pro-oxidative molecules and sometimes enhanced because of the isomerization [14], to high temperature and to light [15,16,17]. Fucoxanthin possesses four isomers, all-trans fucoxanthin, which is the major isomer in the natural environment, 9′-cis fucoxanthin, 13-cis fucoxanthin and 13′-cis fucoxanthin (Figure 2). As it was proven for ß-carotene [18], the cis and trans isomers of fucoxanthin have different anti-oxidant properties. When increasing the temperature, all-trans fucoxanthin changes into the cis isomer and losses 21% of its anti-oxidant potential (measured with DDPH test) [19]. This result was counterbalanced with another later study showing that the difference between an antioxidative potential of the four fucoxanthin isomers is not significant [20]. On the contrary, the cis forms of fucoxanthin from the seaweed Undaria pinnatifida were demonstrated to have better antiproliferative effects against HL-60 cancerous cells, against leukemia cells and Caco-2 (colon cancer) cells [21]. However, the cis forms being more sterically hindered, their bioavailability is lower than trans forms.

3. Biological Function

3.1. In Algae

Fucoxanthin is found in light capture apparatus in the photosystems, as part of the electron chain transport on the thylakoid membrane [22]. It is attached to chlorophylls (a and c) and apoproteins forming complex structures called fucoxanthin-chlorophyll protein complexes (FCP) [23,24]. Due to their particularity of absorbing blue-green spectrum by attaching to chlorophylls, the light-harvesting complexes are capable of a wider light spectrum absorption thanks to fucoxanthin, between 390 and 580 nm [22]. This ability is useful and advantageous for algal cells when there is a lack of red light availability for chlorophylls at certain depths as only blue light can reach further to the cells [23]. Photosynthesis starts with the capture of photons by pigments such as chlorophylls and fucoxanthin, then with the excitation of electrons of the pigments in the photosystem II (PSII) and the subsequent transport of electrons through water splitting at the PSII by various electron carriers in a fixed order. The flow of electrons is passed to plastoquinone, cytochrome b6f, plastocyanin and finally to photosystem I (PSI) to produce NADPH that is used in the Calvin-Benson cycle or the carbon fixation cycle [25]. The role of fucoxanthin in this chain transport is to aid chlorophylls capture light photons more efficiently and to protect the oxidative damage induced by light under high intensity [23,26].
Fucoxanthin molecules were classified for the first time in 2009 into three categories with the study of the diatom Cyclotella meneghiniana, according to their photon absorption capacities [22]. “Fx-blue” are high energy photons absorbing fucoxanthin molecules strictly absorbing in the blue range of the visible light spectrum (λmax = 463 nm). “Fx-green” are intermediate energy photons absorbing fucoxanthin molecules absorbing in a wider blue/green light range (λmax = 492 nm). Finally, “Fx-red” are low energy photons absorbing fucoxanthin molecules additionally absorbing in an even wider blue/green light range called “red-shifted”, range (λmax = 500–550 nm). This specific shift in absorption properties, which is driven by growing conditions, explained the capacity of fucoxanthin to harvest photons over a wide light spectrum [3]. Though these molecules have the exact same molecular structure (there is only one molecule of fucoxanthin), their energetic level and their absorption capacity are intrinsically linked to their binding site on the FCP as was demonstrated by crystallography in the diatom Phaeodactylum tricornutum, which possesses seven fucoxanthin molecules all differentially positioned when bound on the FCP [3]. The overview of several studies concluded that there were, in diatoms, seven fucoxanthin molecules of which two are “Fx-blue”, two are “Fx-green” and three are “Fx-red” [22,27,28,29,30].
Energy transfer from fucoxanthin molecules to Chl a was particularly studied [22]. Like peridinin, a carotenoid specific to some dinoflagellates microalgae [31], the most efficient pathway for energy transfer from fucoxanthin starts with the excited state S1/ICT [28]. This state is a coupling of the fucoxanthin singlet (S1) and the intramolecular charge transfer phenomenon (ICT). With their spatial configuration on the FCP, Fx-red are low energy molecules and therefore the most willing to follow the S1/ICT pathway [22]. This gives Fx-red the ability to be particularly efficient in transferring the incident light energy, in comparison with Fx-blue and Fx-green. Thus, Fx-red is able to capture higher light intensities without creating excess undissipated energy which could generate harmful ROS. Fucoxanthin can therefore be considered, in a way, as photoprotective although it is not its main function contrary to diadinoxanthin and diatoxanthin. More precisely, some fucoxanthin molecules are involved in the quenching of the Chl a triplet (3Chla*) [32]. The quenching is the extinction of fluorescence of the 3Chla* in order for Chl a to reach its fundamental state, it is the dissipation of the excess energy, generating heat. It is a photoprotection mechanism. Those fucoxanthin molecules are the Fx-red, which efficiently transfer the energy from their singlet state S1/ICT to the 3Chla*. Quenching measures of the 3Chla* proved that fucoxanthin definitely plays a role in photoprotection. To corroborate this result, another study on Chaetoceros gracilis supposed that the light capture represents around 60% of the FCP activities and the quenching around 30%, in low light (LL) conditions [33]. LL condition eliminated the possibility of quenching by the Diadinoxanthin/Diatoxanthin photoprotective cycle, only activated in high light (HL) conditions [34]. Furthermore, no Diatoxanthin was found in cells [33]. This result supported the possibility for another type of quenching, by what was previously considered as only photosynthetic pigments such as fucoxanthin. Finally, a crystallographic study confirmed the presence of several fucoxanthin molecules distinctly positioned (i.e., bound) on the FCP, each one being very close to at least one Chl a, substantiating the rapid energy transfer between fucoxanthin and Chl a [3]. Complementary to its photosynthetic property, it was proven that independently from the Diadinoxanthin/Diatoxanthin photoprotective cycle, fucoxanthin also plays a role in photoprotection. This role appears as essential even in LL and would be complementary or in support with the Diadinoxanthin/Diatoxanthin cycle which is not continuously activated in thylakoids.

3.2. In Human

Many review studies have described the properties of fucoxanthin relative to human health [8,35,36,37,38,39] and cosmetics [9,40,41]. Table 1 presents the latest studies of functional activities of fucoxanthin (2020–2021). In particular, studies about cancer inhibition are part of the major fucoxanthin research concepts with the most occurrences in the literature [42]. However, contrary to many studies that demonstrated the anti-cancer properties of fucoxanthin, Terasaki et al. showed that fucoxanthinol, known to be the real active metabolite of fucoxanthin [43], accelerated the growth of human pancreatic cancer cells by up-regulating the expression of key genes [44]. These results are the opposite of what Terasaki et al. previously showed in mice and hamster pancreatic cancer cells as fucoxanthinol induced apoptosis in cancerous cells [45,46]. Another biological activity of fucoxanthin is anti-inflammatory effects in epithelial cells, macrophages, adipocytes, liver cells, lung cells, fibroblasts, and so forth. A study showed that a methanolic extract of the haptophyte microalgae Tisochrysis lutea had a higher anti-inflammatory effect than a pure fucoxanthin extract with the same pigment concentration [47]. Indeed, T. lutea—like Isochrysis galbana, which is a close strain—possesses, in addition to fucoxanthin, several other phenolic compounds that can have anti-inflammatory properties [48]. On the other side, some studies demonstrated that fucoxanthin can have toxic effects on human cells. Fucoxanthin was shown to reduce PC-12 cells’ (neuronal cells) viability at a concentration higher than 5 μM, to reduce 40% of the viability of human lymphocytes in 24 h at a concentration of 10 μM and to be toxic at a concentration of 40 μM in 16 h for keratinocytes [49,50,51].

4. Biosynthesis in Algae

The carotenogenesis pathways among algae are not well known; they were proposed according to their similarity to land plants and based on the chemical structure of carotenoids [97]. The precise biosynthesis of fucoxanthin is currently unknown (Figure 3). However, studies have linked Violaxanthine De-Epoxidase (VDE) to the regulation of fucoxanthin production. Kwon et al. showed a correlation between a higher fucoxanthin synthesis and a higher VDE expression, along with a higher expression of the ISPD gene, in the diatom P. tricornutum [98]. According to their results, these two genes are critical genes for the regulation of fucoxanthin biosynthesis in P. tricornutum. VDE is likely to be part of the upstream regulation of fucoxanthin as it is known to interfere in the de-epoxidation of violaxanthin into antheraxanthin [97]. Furthermore, an enzyme participating in the biosynthesis of fucoxanthin has been characterized by Gaidarenko et al. in the diatom Thalassiosira pseudonana, encoded by the Violaxanthine De-Epoxydase Like gene (VDEL) [99]. When the gene was up-regulated, the fucoxanthin content increased and reversely, pigments from the photoprotection cycle such as Diadinoxanthin and Diatoxanthin logically decreased. According to this study, and because the VDEL gene is present in five other diatom species (Thalassiosira oceanica, Cyclotella cryptica, Phaeodactylum tricornutum, Fragilariopsis cylindrus, Pseudo-nitzschia multiseries), this result is supposed to apply to all diatoms. Based on the assumption of Lohr and Wilhem in 2001, arguing that the violaxanthin was a precursor of Diadinoxanthin, Diatoxanthin and fucoxanthin [100], it is likely that the VDEL enzyme influences not only the violaxanthin content but also the Diadinoxanthin, Diatoxanthin and fucoxanthin content, strengthening the results and the hypothesis of Gaidarenko et al. Furthermore, another research team confirmed the VDEL enzyme is responsible for the central reaction converting the violaxanthin into neoxanthin in Chromista (clade containing diatoms, haptophytes and brown seaweeds) [101]. They also supposed Diadinoxanthin to be an intermediate between neoxanthin and fucoxanthin in contrary with another study assuming that fucoxanthin is synthesized directly from neoxanthin [38], despite the fact that the corresponding enzymes have not been characterized yet. In both cases, the VDEL enzyme could indirectly regulate the production of fucoxanthin (Figure 3). However, in the haptophyte microalgae T. lutea, which is one of the most interesting species for fucoxanthin production, no neoxanthin has been found so far [102,103]. It indicates that neoxanthin cannot be considered as a precursor of fucoxanthin in all Chromista species.
A study also highlighted the role of the MET pathway (methylerythritol phosphate pathway) in the accumulation of fucoxanthin in P. tricornutum [104]. Indeed, the research team showed that both CMK and CMS genes, involved in the MEP pathway, enhanced the fucoxanthin content in P. tricornutum by increasing the photosynthetic efficiency, and by redirecting the metabolic precursors towards fucoxanthin biosynthesis from the lipogenic pathway [104]. Thus, the MET pathway is not directly involved in fucoxanthin biosynthesis but it allows a greater accumulation of this pigment in P. tricornutum.

5. Bioavailability

Two decades ago, the fate of the degradation products of carotenoids in the human body was unknown [105]. Then, the beneficial effects of some carotenoid metabolites were demonstrated, which motivated further research on this subject. For example, it is the case with fucoxanthin which is mainly ingested through food consumption of macroalgae such as brown seaweeds Undaria and Laminaria in Japan. Finally, researchers came to understand that the interest of fucoxanthin lays in its bioavailability (the measurement of the rate and speed of absorption by cells) and its metabolization. In mammals, fucoxanthin is first metabolized into fucoxanthinol, then into amarouciaxanthin A [106].
More precisely, once ingested, fucoxanthin is hydrolyzed in fucoxanthinol in the intestinal tract. Then, fucoxanthinol is absorbed by intestinal cells and carried to blood vessels, suggested that the bioavailability of fucoxanthin is indeed based on that of fucoxanthinol in mammals [43]. A study discovered that in some murine liver cells, fucoxanthinol was then metabolized into another molecule, amarouciaxanthin A. This suggestion was then demonstrated on a larger scale by other studies, proving moreover that fucoxanthinol and amarouciaxanthin A were detected in many tissues (plasma, erythrocytes, liver, kidneys, heart, spleen for fucoxanthinol, and adipose tissue for amarouciaxanthin A), unlike fucoxanthin, except for a few traces, simply meaning that a tiny part had not been metabolized [107,108].

6. Producing Species

6.1. Best Producers

Many algae species are known for their fucoxanthin content in the cell membranes that can be extracted. The current commercial production of fucoxanthin is based on brown seaweeds (macroalgae) [109]. Macroalgae produce fucoxanthin in varying amounts depending on the species and their metabolism. The content may vary from 0,02 to 4,96 mg·g−1 in fresh samples of different species (the maximum was reached in Undaria pinnatifida) and 0,01–2,08 mg·g−1 in dried samples of different species [39]. The concentration of macroalgal fucoxanthin is thus very low and not sufficient for the global demand of this potential nutraceutical compound. Microalgae, on the other hand, show to be a great source of fucoxanthin as they are fast-growth microorganisms and their fucoxanthin content is high. Diatoms and haptophytes are the most promising groups of microalgae for the commercial production of fucoxanthin [109]. For example, the fucoxanthin content can reach as unusually high as 59.2 mg·g−1 in dried samples of the diatom P. tricornutum [110] and 79.40 mg·g−1 in dried samples of the haptophyte T. lutea [111] in batch culture under optimized conditions. Diatoms accumulate fucoxanthin in large amounts and have already been widely studied and exploited for fucoxanthin production. Two microalgal diatom species and one haptophyte were identified to produce a very high amount of fucoxanthin, P. tricornutum, Odontella aurita, and Isochrysis aff. galbana (T. lutea), respectively [39]. These species have been an extensive target study for fucoxanthin production and optimization for higher productivity in the literature. Table 2 lists some of the species of microalgae that produce fucoxanthin from studies between 2020 and 2022.
At an industrial scale, the main objective is to optimize the production costs constituting the greatest expenses like the labor, energy and chemical supplements [137]. For example, the cost of a culture of P. tricornutum required for an equivalent organic weight is four times lower than the other diatom Chaetoceros gracilis in hatcheries production [138]. In general, diatoms and haptophytes represent popular species because they are easy to cultivate and can reach a high amount of biomass in a short time. P. tricornutum can reach, for instance, a biomass productivity of 1500 mg·L−1·day−1 in an outdoor helical reactor [139]; Thalassosira Weissflogii can reach 538 mg·L−1·day−1 in a tanks reactor [130]; and T. lutea can reach 940 mg·L−1·day−1 [112] and 350 mg·L−1·day−1 [114] in 400 mL photobioreactor. Even if most studies are with diatom species in literature, the cultivation of haptophyte species represents a certain advantage in fucoxanthin extraction processes. Indeed, diatoms possess a silica frustule which necessitates an additional step in the extraction process to remove it, whereas non-coccolithophore haptophytes, like T. lutea and Pavlova lutheri, do not possess one, which eases the extraction of fucoxanthin in the downstream processing [140,141]. T. lutea especially is part of the best fucoxanthin producers [39,118]. This species is well known as it is widely used in live feed in aquaculture [142,143] as it possesses valuable nutritional properties attributed to its capacity to accumulate lipids and produce carotenoids [144,145]. Furthermore, T. lutea is able to achieve high biomass with high fucoxanthin concentration in a short period of cultivation (between 6 to 15 days). In addition, the culture can be carried out with sustainable and low-risk resources [39,102]. With mild growth culture conditions such as a wide range of light irradiances and temperatures [146,147,148], T. lutea is definitely easier to cultivate than other microalgae species.

6.2. Measurement of Fucoxanthin

In some studies with a further purpose of the continuous production of microalgae, such as the larvae feeding for example [149], it is common to measure the pigment’s productivity (e.g., mg.L−1.day−1), also referred to as the production rate or volumetric productivity. The objective is to express the effectiveness of the production of a valuable pigment by combining two main factors being the pigment content in cells and the biomass growth in terms of time and cell density.
However, when the objective is to better understand how to improve the pigment content, by cells, of an algae species, therefore excluding the contribution of the amount of biomass, it is more appropriate to measure the production in mg.g−1 or in fg.cell−1, also referred as the specific pigment concentration. Indeed, even in a further industrial purpose, the first step is to study the physiology of the algae species as the production of valuable metabolites such as carotenoids often results from stress modifying their metabolism (nutrients, light, temperature, etc.) [104,128,146,150]. Some studies express the pigment production in mg.L−1, also referred as the volumetric concentration, which depends on two factors being the pigment content and the biomass in terms of cell density only. This measure is not suitable to describe the physiology of algae cells, as it is not normalized by the cell density. A higher fucoxanthin production in mg.L−1 does not necessarily imply that cells produce more fucoxanthin, it might just be the result of an increase of the biomass. However, this measure can be used to compare the production of fucoxanthin in several cultures in batch culturing mode for example.
A lot of studies gather the information by displaying both productivity and production measures. This way to present results allows to consider the influence of the culture conditions simultaneously on the cell metabolism and the relative growth of the studied species (Table 2).

7. Culture

7.1. Reactors, Temperature, pH and Salinity

Microalgal cultivation has been traditionally operated with open systems such as the open tank and raceway ponds [151]. The open ponds are easy to construct and operate with low cost for mass production of microalgae [152], but also for fucoxanthin production as it has been shown for P. tricornutum cultivated in the open pond [153]. However, they pose a risk of limited control of cultures towards the progressive changes of the surrounding environment such as contamination, incremental increase of salinity, the problem of mass transfer and loss of nutrients through evaporation [154]. These drawbacks have shifted interest in microalgae cultivation towards the use of more performant, more controlled close systems, the photobioreactors (PBRs) (Figure 4). The most used PBRs are tubulars, stirred tanks and flat panels. Among them, flat panels are the most preferred in literature [117,155,156,157], and even more to study the specific response of microalgae to light. Indeed, they have a high surface area to volume ratio, and even if the area required for such reactors might be inconvenient at industrial scale, there are advantages. A flat panel reactor permits higher light absorption and reduces the effect of self-shadowing caused by the microalgal growth. Therefore, it allows greater biomass production. On the other hand, as cells produce more fucoxanthin in low light, self-shadowing can also be of interest. Even if it still happens when culture in flat panels reach high concentration, a lack of an early self-shadowing can be inconvenient for fucoxanthin accumulation. The balance between biomass and fucoxanthin accumulation is essential. In addition, the low oxygen accumulation in flat panel reactors prevents the growth of contaminated aerobic microorganisms, reinforced by the easiness of sterilization and the flexible structures [158,159]. A study by Derwenkus et al. analyzed the cost of scaling-up production of both EPA and fucoxanthin in flat-panel airlift PBRs and concluded that the profitability of the process mostly depended on the fucoxanthin market price [122]. For fucoxanthin production, batch cultures are often operated with a short residence time that is less than 15 days [110,121,158,159,160,161]. Fucoxanthin productivity takes into account both the daily production of pigments and the growth of microalgae. It is thus commonly associated with the continuous modes after optimization of the culture parameters [114,121,122,152].
Temperature in the reactor also affects the productivity of fucoxanthin as it is linked to biomass growth. Depending on cultivated species, the optimal temperature can vary in the mesophilic range (30 °C for T. lutea, 22 °C for P. tricornutum, 23 °C for Cylindrotheca fusiformis) [114,160,161]. pH was shown to have an influence on fucoxanthin accumulation in P. tricornutum as fucoxanthin is sensitive to low pH media [26]. Wu et al. demonstrated the impact of flocculants, the common microalgae harvesting agents, on the fucoxanthin content of species [162]. The use of a high dose of flocculants increases the recovery rate of biomass but caused a significant reduction of fucoxanthin due to low pH and detrimental effects associated with high valent metallic ions such as aluminum [24]. All of the current most performant species for high fucoxanthin production are marine microalgae whose growth depends on the salinity of the medium which acts as osmotic control of metabolites. The study of Ishika et al. showed that P. tricornutum grew well and produced more fucoxanthin at optimal salinity of 45‰, while halophile microalgae accumulated more fucoxanthin at up to 77‰ [152]. Fucoxanthin plays an important role in carbon fixation during photosynthesis and thus has been found to be affected by the mass transfer of carbon [26,110,162]. Agitation and aeration in the reactor could increase the fucoxanthin content and reduce the harvesting time by half as demonstrated in the work of Bauer et al. [26].

7.2. Light

One of the most important parameters for fucoxanthin production and productivity is the light condition. Various studies have demonstrated the influence of light wavelength, intensity and the light-darkness cycle on the accumulation of fucoxanthin. Studies have shown that low light intensity (less than 100 mol.m−2.s−1) promotes the fucoxanthin production [39,114,120,163,164] while high light intensity (starting from 150 mol.m−2.s−1) can damage the photosystems, therefore activates the production of photo-protective pigments (Diadinoxanthin and Diatoxanthin) [165,166]. Moreover, as more photons are available, cells do not need to capture more photons than necessary due to photon saturation and hence do not produce more chlorophylls and fucoxanthin [167]. Indeed, in the high light regime, not only fucoxanthin degrades [168] but there is also a change of ratio among the photoprotective and the photosynthetic cell pigment content (xanthophylls, carotenoids, chlorophylls). The metabolism behind this is revealed in the violaxanthin and diadinoxanthin cycles that control the production of zeaxanthin and diatoxanthin under high light intensity [169]. In that case, fucoxanthin content is reduced while zeaxanthin, and diatoxanthin, the photoprotective pigments, are accumulated to protect the photosystem [34,163,165,170,171,172].
The increase of fucoxanthin in the low light regime is ascribed to the compensation of low light radiance as fucoxanthin is a part of the light-harvesting antenna that promotes the photon capture for photosynthesis. However, biomass production is found to be inversely proportional to fucoxanthin production as high light promotes the development of the biomass [120]. An improved fucoxanthin productivity results therefore, for each producing species, of a compromise between a high light that allows a great biomass production, and a low light that increases the fucoxanthin production. For example, in cultures of T. lutea, the highest fucoxanthin productivity (9.81 mg·L−1·day−1) was achieved at 300 mol·m−2·s−1 while the highest fucoxanthin content (5.24 mg·g−1) was achieved at 150 mol·m−2·s−1 [114]. In cultures of the haptophyte Isochrysis zhangjiangensis, the highest fucoxanthin productivity (3.06 mg·L−1·day−1) was achieved at 100 mol·m−2·s−1 while the highest production (22.6 mg·g−1) was achieved at 40 mol·m−2·s−1 [120].
Fucoxanthin absorbs blue-green light and thus has shown, in diatoms, to be accumulated in blue light even at high intensity while red light favor the production of other pigments such as diadinoxanthin [121,161]. Furthermore, in the diatom Cylindrotheca closterium, red light and green light decreased the fucoxanthin content because of the lack of blue light [173]. In T. lutea, the highest fucoxanthin content was found in blue-green light while the highest fucoxanthin productivity was found in red-blue-green light (which is closer to white light) [116]. The accumulation of fucoxanthin in blue-green light was expected, as this spectrum is prevalent in the natural habitat of brown algae [3]. Indeed, the absorbance spectrum of fucoxanthin ranges from 450 to 540 nm in solution [174]. This range is even wider, between 390 and 580 nm, once the fucoxanthin is bound to a FCP [22].

7.3. Nutrients

Nutrients play an important role in microalgae growth as they are required to synthesize lipids and macromolecules such as nucleic acids and proteins that are essential for algal cells [175]. Nitrate, phosphate, iron, and silicate (for diatoms) have been identified in various studies as nutrients that have an impact on cells growth and on biomass accumulation [26,135,158,161,162,176].

7.3.1. Nitrogen

Nitrogen is vital to microalgae as it is incorporated into macromolecules such as proteins, enzymes and nucleic acids, which have a structural or functioning role in cells. Nitrogen can be supplied from an inorganic source either as ammonium or nitrate [135,176,177]. Nitrate is the main form of oxidized nitrogen which accumulates in algae [178]. Subsequently, nitrate is converted into ammonium which is easier to be assimilated into large molecules through transamination in the anabolic pathways [179]. Nevertheless, ammonium when used as a feeding source decreases the pH medium [180], which can hamper the growth of microalgae due to pH-sensitive proteins and enzymes. Many studies have demonstrated the strong correlation between nitrate concentration and biomass production, which indicates nitrogen is one of the limiting factors for biomass production [181,182,183,184,185,186]. High nitrate content promotes the growth of microalgae while a low concentration of nitrate inhibits the growth. Nitrate also has an influence on the pigment content as porphyrins, the core of chlorophylls, contain nitrogen [26,158]. The study investigated by Gao et al. showed the positive linear correlation between chlorophyll and fucoxanthin in T. lutea, which explains the indirect dependence of fucoxanthin on the nitrate concentration in the medium [115]. Studies have shown high dependence of fucoxanthin on nitrate concentration in various microalgae species. However, in batch culturing mode, a higher nitrate concentration can lead to a higher biomass concentration which induces the self-shading of the cells. With less access to incident light, the photosynthetic pigments such as fucoxanthin are increased. Therefore, in some studies with batch culturing mode, higher fucoxanthin concentration is linked to higher biomass and not directly to a higher nitrate concentration [110,184,185,186,187]. In Xia et al. however, two batch mode cultures with 6mM and 18mM of nitrogen respectively resulted in the same biomass concentration after 12 days of culture in low light, but the 18mM nitrogen culture resulted in the highest fucoxanthin content [155]. In this case, we can effectively attribute the increase in fucoxanthin content to a higher nitrogen concentration. As to fucoxanthin production, in mg·L−1, or fucoxanthin productivity, in mg·L−1·day−1, it is effectively promoted at high nitrate level due to the increase of the biomass, while too low nitrate causes a decline [110,111,160]. Xia et al. investigated the effect of the initial concentration of nitrate as a feeding source on fucoxanthin content [188]. The initial high concentration of nitrate boosts the accumulation of fucoxanthin in the chloroplast membranes compared to the initial low nitrate. Furthermore, initial high nitrate coupled with nitrogen supplement increases fucoxanthin content more than four-fold as much as only using initial low nitrate [141]. Supplement of nitrogen has been demonstrated to augment two-fold or up to three-fold fucoxanthin content in P. tricornutum [110]. On the contrary, nitrogen deficiency induces the degradation of compounds containing nitrogen like proteins and chlorophylls, and therefore decreases the photosynthetic capacities [189].
Further investigation showed the medium type also influences the fucoxanthin accumulation in microalgae [26,190]. Conway medium was shown to be more effective than f/2 medium in inducing fucoxanthin production in the work of Gómez-Loredo et al. [176]. The high performance of Conway medium is due to a higher concentration of nitrate which is sufficient for microalgae to keep high content of fucoxanthin during the whole cultivation period [110,176]. Nitrate influence on fucoxanthin has been found further to be a synergic effect with light and salinity [188]. Combination of both light availability and nitrate level can increase further fucoxanthin quantity in Cyclotella cryptica and an increase of both the nitrate level and the salinity at optimal conditions enhances fucoxanthin content in T. lutea [111]. The synergic effect of nitrate level on fucoxanthin could be exploited further for high production of fucoxanthin.

7.3.2. Phosphorus

Phosphorus is essential for microalgae as it is a part of the backbone of nucleic acids and ATP, the energy carrier of cells, and phospholipids [175]. Contrary to nitrogen, phosphorus does not have a high influence on biomass growth and fucoxanthin accumulation as shown in the work of Lu et al. and Sun et al. [141,161]. Very few studies have demonstrated the correlation between phosphorus and fucoxanthin content in contrast to the well-documented nitrogen influence [141,161].

7.3.3. Silicate

In diatoms, another important nutrient is silicate which is required for cell growth as the cell wall contains silicon. Therefore, silicate availability is linked to the morphology of the diatom cells which can have impacts on cell growth and eventually fucoxanthin content [133]. High silicate level promotes the growth of both biomass and fucoxanthin accumulation in diatoms [133,134,191]. The enhancement of fucoxanthin is due to the upregulation of metabolism and cell cycle progression associated with silicate in marine diatoms [133]. The study of Mao et al. showed that at a high level, silicate induces the accumulation of fucoxanthin but at a low level it suppresses the fucoxanthin production [133].

7.3.4. Carbon

Mixotrophy is considered the mixed condition between photoautotrophy and heterotrophy. In mixotrophy, microalgae can use either light or organic carbon as energy sources and carbon sources can be supplied through carbon dioxide sequestration or from organic sources [192,193]. The ease of shifting towards different sources makes the algae more independent of light, which does not limit the culture growth as in autotrophy and assimilation of carbon can be supported by organic substances similar to heterotrophy. By taking advantage of both photoautotrophic and heterotrophic modes, mixotrophy utilizes the resources more efficiently and for high biomass production. As for nitrogen, a higher biomass may induce the self-shading of cells and subsequently may enhance the production of photosynthetic pigments such as fucoxanthin. Alkhamis et al. reported a two and a half times increase of fucoxanthin content in the mixotrophic culture of T. lutea (11.5 mg·g−1 DW) compared with the phototrophic culture (4.8 mg·g−1 DW) [146]. In a mixotrophic culture of the diatom Nitzschia laevis, the fucoxanthin content reached 15.6 mg·g−1 DW while in heterotrophic culture it reached 10 mg·g−1 DW [194]. Mixotrophic cultures of P. tricornutum have been investigated on the high accumulation of fucoxanthin in microalgae and have shown promising results for both biomass and fucoxanthin production, which can be optimized for optimal production of the xanthophyll pigment [121]. These results prove that the mixotrophic cultivation strategies for some microalgae could be more suitable for both biomass and fucoxanthin accumulation. At an industrial scale, one limit of the mixotrophy culture could be the cost of the organic carbon source that is used (glycerol, starch, spruce hydrolysates) [195,196,197].

8. Extraction and Purification

8.1. Ultrasound Pretreatment

Because fucoxanthin is attached to proteins and other pigments such as chlorophylls in the light-harvesting system anchored inside the membrane, its extraction is improved when pretreatment of algal biomass is conducted prior to or during extraction [198,199,200]. Especially, diatoms possess a thick cell wall made of silica that needs to be disrupted to achieve an efficient fucoxanthin extraction. The degradation of cell walls and membranes can be achieved either by mechanical, chemical, thermochemical, biological or electromagnetic methods [201]. In contrast, the haptophyte microalgae T. lutea does not possess a silica cell wall. Therefore, this species is not only one of the best producers but is also advantageous for fucoxanthin extraction as it does not require a specific pretreatment. Ultrasound (US) treatment can however be implemented to enhance the extraction step [103].

8.2. Conventional Solvents

Fucoxanthin is often extracted with conventional methods using organic solvents or water such as maceration [198,202]. As fucoxanthin contains oxygen and other polar functional groups, its extraction is conducted with medium polarity solvents such as ethanol, acetone, and so forth. Although water has a high dielectric constant, fucoxanthin is barely extracted with hydrotreatment [202,203]. Guler et al. showed that a mixture of tetrahydrofuran and dichloromethane is the best solvent system for fucoxanthin separation from the membrane, but these solvents have a high risk of flammability and explosion (formation of peroxide in presence of air or tetrahydrofuran) [203]. However, two alcohols are often preferred for fucoxanthin extraction. These are methanol and ethanol, which are less toxic compared with tetrahydrofuran and dichloromethane. Indeed, they are safer to use and have shown to have superior performance over carbonyls compounds such as acetone (only one-third yield compared to ethanol) and ethyl acetate (one-sixth compared to ethanol) [13,155,199,202,203]. Due to toxicity and environmental issues linked to methanol, ethanol is preferred and has been demonstrated to extract fucoxanthin efficiently at moderate temperature [13,202,204]. Although the conventional solvents were proven to efficiently extract and recover the carotenoid, they are often time-consuming and require a substantial amount of solvents to be able to remove fucoxanthin from the light-harvesting system attached to the membrane.

8.3. Microwave, US, Pressurized Liquid, Enzyme, Sub and Supercritical Fluid, Electrotechnology

Accelerated extraction methods can be listed as follows: microwave-assisted extraction [201,205,206], ultrasound-assisted extraction [198,205], pressurized liquid extraction [198,207,208], high pressure homogenization [209,210] and enzymatic-assisted extraction [211]. They provide rapid and efficient extraction which can preserve pigments without structure modification due to prolonged contact at high temperature. Subcritical and supercritical fluids have also been considered as they have high recovery in fucoxanthin and are more environment-friendly due to less consumed amount of organic solvents, easy to be removed and the use of non-toxic supercritical carbon dioxide but they present lower selectivity among the pigments and higher operation cost as main drawbacks [199,202,203,212]. Electrotechnologies-assisted methods, such as pulsed electric field [213,214], moderate electric field [215], high-voltage electric discharges [216] and electropermeabilization-assisted liquid biphasic flotation [217], provide a good extraction of intracellular components by delivering electric current and allowing an electroporation which increases solvent permeability and hence increases pigment extraction efficiency [218]. However, no studies have been conducted to extract fucoxanthin neither from macroalgae nor microalgae using these advanced methods [202].

8.4. Bio-Based Solvents

8.4.1. Edible Oil

Due to the use of petrochemical and toxic organic solvents for extraction, bio-based solvents have been proposed such as edible oils, ionic liquids and natural deep eutectic mixtures [199]. Edible oils have the advantage to be already accepted by the consumer, being non-toxic, bio-based and eco-friendly [199]. To our knowledge, only one study reported the effective extraction of fucoxanthin with edible oil from Sargassum horneri [219]. The best extraction rate was achieved with short and medium-chain triacylglycerols (SCT and MCT). Indeed, as the main inconvenient of using edible oil is their high viscosity due to carbon chain, thus preventing the diffusion of carotenoids into the oil, it is better to select oils with a minimum number of carbons such as SCT and MCT (from C3 to C8) [219]. Furthermore, it was demonstrated that the absorption rate and thus the bioavailability of fucoxanthin was enhanced when the ingestion was supplemented with MCT from fish oil [220].

8.4.2. Ionic Liquids

Ionic liquids are also considered for a more eco-friendly extraction of fucoxanthin. Ionic liquids are solutions of salt with a melting point close to or under ambient temperature, they release anions and/or cations that interact with solutes. So far, the imidazolium-based, the ammonium-based and the phosphonium-based ionic liquids are the most current, though this extraction technique is emerging [221]. In addition to the fact that these solvents are effective at a relatively low temperature, they are non-volatiles. However, they are not bio-based and their cost price is high, hence the need to recycle them by crystallization for example. Table 3 presents some carotenoids extractions using ionic liquids.

8.4.3. Natural Deep Eutectic Solvents

Finally, natural deep eutectic solvents (NADES) are another promising alternative to volatile organic solvents. They are considered as eco-friendly because they are non-toxic, biodegradable and recyclable [223,224]. NADES are composed of two or more natural pure compounds which, together, behave like a unique and pure compound. They have been used for the extraction of astaxanthin, a carotenoid [225]. To our knowledge, in the available literature, there exists only one study suggesting the use of NADES for fucoxanthin extraction from brown algae—Fucus vesiculosus [226], combined with ultrasound-assisted extraction (although this step is necessary for macroalgae, it might not be for a non-calcifying microalgae). The research team used one NADES composed of lactic acid and choline chloride (3:1 molar rate), and another one composed of lactic acid, glucose and H2O (5:1:3 molar rate). They further analyze the anti-oxidant activity of fucoxanthin, which was not altered by the extraction process. Their results highlighted a great potential for the extraction of fucoxanthin.
In conclusion, conventional solvents such as acetone and ethanol are currently the most used for fucoxanthin extraction, with a preference for ethanol. However, for a few years, more eco-friendly extraction methods are tested for a high recovery of fucoxanthin, one of the most promising being the NADES extraction.

8.5. HPLC and Supercritical Anti-Solvent

Gallego et al. (2020) investigated the simultaneous pressurized liquid extraction and purification with adsorbents during extraction of fucoxanthin from T. lutea [227]. Results from high-performance liquid chromatography (HPLC) and mass spectroscopy showed that chlorophylls and other xanthophylls are effectively retained by adsorbents and removed from pigment extracts which left only fucoxanthin as the main component although no purity was specified [227]. Chen et al. considered a green process using supercritical anti-solvent fucoxanthin crystallization from H. mitchellae using supercritical carbon dioxide with a high recovery and purity of fucoxanthin of 98.3% and 87.7%, respectively [228]. Despite the benefits and advantages of these new methods that utilize less toxic solvent and are less time-consuming compared to traditional procedures, the chromatography systems still remain the most efficient method for purification following extraction.

8.6. Aqueous Two-Phase System

Other promising and potential methods are alcohol-salt aqueous two-phases systems (ATPS) or coupling ATPS with ultrafiltration [229,230]. Indeed, these methods are considered eco-friendly as they imply the use of aqueous non-polluting solvents. ATPS is based on the difference of partition coefficient of fucoxanthin between the two immiscible solvents, water being the main component of both phases [231,232,233]. There exist different types of ATPS, the most common being the polymer-polymer system (polyethylene glycol, dextran) [234,235] and the polymer-salt system (phosphate, sulfate, citrate) [236,237]. Other types include the alcohol-salt systems (ethanol, propanol) [238], the micellar/reverse micellar system, the ionic liquids system (imidazolium). In particular, Gómez-Loredo et al. managed to purify fucoxanthin with an alcohol-salt system made of ethanol-K2HPO4 [239]. They obtained 95.36% of recovery and 66.01% purity for fucoxanthin extracted from P. tricornutum and 89.18% recovery and 78.14% purity for fucoxanthin extracted from I. galbana [239].

8.7. Centrifugal Partition Chromatography

One of the advanced methods has made the purity of fucoxanthin higher than 99% feasible with centrifugal partition chromatography (CPC), after extraction of fucoxanthin with conventional solvent or other methods [103]. The principle of CPC is based on the difference of partition of solutes between two immiscible liquids, which can enrich fucoxanthin and remove most of the impurities [103]. The advantages attributed to CPC compared to silica gel column are that it does not generate polluted silica particles, does not require a high amount of solvents and provides a fast and complete sample recovering without degradation [103]. This technique has made highly purified fucoxanthin feasible and attainable for its eventual applications in food and drugs, and has removed the purification limit of fucoxanthin that was previously only attainable at 99% with tedious procedures [103]. Figure 5 illustrates a purification process of fucoxanthin using CPC method for T. lutea culture. There are only two reports for the purification of fucoxanthin so far in the literature to our knowledge [103,240]. According to the study of Gonçalves de Oliveira Junior et al., their first results with T. lutea validate the use of CPC as an eco-friendly method for very efficient extraction and pre-purification of fucoxanthin from microalgae. Furthermore, they are convinced that the separation conditions can be optimized.
In addition, all the fucoxanthin extraction methods do not lead to the same purity. Some methods require long and stepwise treatment that increase the impurity content while others are operated at a prolonged high temperature which may cause fucoxanthin degradation. Other influencing factors that induce fucoxanthin decomposition include low pH solution, exposure to light which have to be considered when the purification step is conducted.
To be able to be used in pharmaceuticals and nutraceuticals, high purity of fucoxanthin is demanded. Oral studies for fucoxanthin activities and toxicity employ a minimum content of 95% fucoxanthin to reduce side effects of impurities [241,242]. Toxicological studies showed that there are known negative effects of fucoxanthin at high concentrations on human cells’ viability such as neuronal cells (PC-12 cells) and keratinocytes (HaCaT). Thus, fucoxanthin purity and concentration need to be monitored [49]. Only the work of Alghazwi et al. specified the purity of fucoxanthin, which is 95%, and its limit concentration to cause toxicity [49].

8.8. Stability of Fucoxanthin

Due to the extended conjugated system of double bonds, fucoxanthin is susceptible to isomerism during processing [20,243]. Furthermore, large scale production, stability and long-term storage of fucoxanthin is of importance. Fucoxanthin has been reported to be quite unstable after its removal from the biomass under external conditions such as light, presence of oxygen, high temperature, low pH media and water presence [13,19,26,244]. Fucoxanthin has been known to be easily damaged in water at 26 °C with 30% loss after four weeks [244]. Due to these reasons, fucoxanthin degradation is possible and can be significant in extraction and purification steps. New methods that operate at lower temperatures, lower pressures and avoid long residence time are thus required. A further alternative could be to integrate an anaerobic method to avoid oxidation damage. Another problem of fucoxanthin in applications in pharmaceuticals and nutraceuticals is that fucoxanthin has low bioaccessibility due to low solubility in water and due to its degradation into fucoxanthinol in the case of direct consumption [244]. Encapsulation of fucoxanthin has been well studied to conserve the structure of the xanthophyll and increases its stability as well as its bioavailability [209,210]. Edible materials with high performance such as fatty acids, porous starch, casein, chitosan, gold, have been used to encapsulate fucoxanthin in the form of micro or nanoparticles and showed the improved activity and stability as well as bioaccessibility of fucoxanthin [162,244,245,246,247,248,249,250,251,252,253]. The balance between a preserved stability and an improved activity of fucoxanthin induces a higher cost of the production process due to the complexity of the encapsulation.

9. Global Market of Fucoxanthin

The multiple studies on fucoxanthin demonstrated that this pigment is an eco-friendly alternative, as a natural ingredient, to food complements, cosmetic compounds and medicines (Figure 6). Because of its unusual chemical structure, the chemical synthesis of the fucoxanthin molecule is not yet possible. Currently, the commercial sources of fucoxanthin for food are brown seaweeds such as Laminaria sp. (known as Saccharina sp.), Sargassum sp., Fucus sp., Undaria pinnatifida and Hijka fusiformis [254]. Fucoxanthin is currently mostly sold in Asia (Figure 6) as brown seaweed powder or oil mostly in capsule or cachet, presented as a fucoxanthin concentrate or in combination with poly-unsaturated fatty acids which are high-value components too. An important number of Asian companies are already major actors in the market (Oryza Oil and Fat Chemical Co., Yangling Ciyuan Biotech Co., Yigeda Bio-Technology Co., Agrochemi Co., etc.). The Novel Food Regulation in Europe authorizes the consumption of the macroalgae species previously described, whereas it authorizes only one fucoxanthin-producing microalgae so far, the diatom O. aurita [255]. However, O. aurita is currently sold as an organic silicium complement, not as a fucoxanthin concentrate, and only two companies are reported to propose such products to our knowledge (Algosud and Motima Laboratory). In the United States, more products derived from microalgae have been authorized for the market (Figure 6): FucovitalTM by Algatech, NutriXanthinTM and DermaXanthinTM by Algahealth, BrainPhytTM and PhaeosolTM by Microphyt (which obtained in 2019 the status of New Dietary Ingredient from the American Food and Drug Administration). Furthermore, although some microalgae are great fucoxanthin producers (diatoms and haptophytes), no extraction method has been standardized yet [40]. It represents a major challenge for fucoxanthin to be considered as an economic natural ingredient, as it should be obtained by using simple, fast, and low-cost technologies methods [40]. However, the current unrestricted consumption of fucoxanthin as a dietary supplement, easily accessible online, is an issue. Indeed, a significant number of products are mislabeled/misbranded, highlighting the need for a more stringent regulation [256].
Fucoxanthin represents an important market as a nutraceutical for its numerous health properties (anti-oxidant, anti-cancer, anti-diabetes, etc.) [257], in medicine, and also in cosmetics (Figure 6). Indeed, although it is only a secondary market for now, the bioactivities of fucoxanthin demonstrated so far for the cosmetic industry are anti-aging, anti-wrinkle, anti-UV-induced oxidative stress [9,258,259]. These properties are mainly due to the anti-oxidant activity of the molecule, which prevents from the formation of reactive-oxygenic species (ROS). Indeed, oxidative stress plays an important role in the wrinkle formation process by causing the degradation of collagen matrix and therefore wrinkles [260]. Furthermore, it is known that the UCP1 protein (uncoupling protein 1) prevents the accumulation of adipocytes specifically in brown adipose tissue. In vivo studies on mouse models suggest that fucoxanthin allows the expression of UCP1 in white adipose tissue [261,262], which is the major fatty tissue of adult humans, especially in obesity cases where the brown adipose tissue is atrophied [263]. The UCP1 would then prevent the accumulation of fat, reducing the fat mass of white adipose tissue. Provital, a Spanish company, performed a study demonstrating that after the application of fucoxanthin enriched cream-gel on fatty tissues in 61 volunteers, the fat layer and cellulite were reduced [264]. In response to the increased interest of this carotenoid, the annual growth rate of the current market of fucoxanthin as a nutraceutical or cosmetic ingredient is +2.47% in average. The market size of fucoxanthin was 92 million $ in 2014, 99 million $ in 2017, and is expected to reach US$ 120 million by 2022 [40,265]. Derwenkus et al. concluded that the profitability of the process to obtain fucoxanthin mostly depended on the fucoxanthin market price [122]. They also highlighted the fact that the biomass production cost of microalgae is lower in higher culture volume (from 882 €/kg to 228 €/kg from 0.7 t/year to 170 t/year).

10. Perspectives and Conclusions

Along with other photosynthetic and photoprotective pigments, fucoxanthin is bound to the Fucoxanthin Chlorophyll a/c binding Protein and forms the light-harvesting antenna in the chloroplasts of brown macroalgae and microalgae. In addition to its main role of capturing photons, fucoxanthin is a strong anti-oxidant in algal cells by limiting the formation of reactive oxygen species. This property is also exploited in human health, as well as anti-cancer, anti-inflammatory, anti-diabetic and anti-obesity properties. As fucoxanthin cannot currently be artificially synthesized, its production lays on brown algae. The best producers are microalgae, and especially Tisochrysis lutea, Phaeodactylum tricornutum, Odontella aurita. These species are relatively easy to grow as they do not require very specific culture conditions apart from main nutrients (nitrogen, phosphorus, silicate). The main challenge for fucoxanthin production is the design of the photobioreactor, which has to meet several requirements. Cells need to have enough access to light to grow but the irradiance must be low enough to avoid photoinhibition and encourage fucoxanthin accumulation. Furthermore, the reactor must be sufficiently aerated to provide the best balance between oxygen and CO2 and adjust the culture pH to its optimum. Currently, the most popular reactor in the literature is the flat-panel photobioreactor which provides homogeneous access to light, but whose main issue is to require a great area for a small culture volume. It can be an important inconvenient at industrial scale.
The downstream processes to extract fucoxanthin from the culture became a real challenge as they must respect a maximum of green chemistry principles to last in the future. Over the last years, several techniques were tested such as the microwave extraction, the pressurized liquid extraction, the sub and supercritical fluid extraction. These are promising techniques, and more studies will be performed in the years to come, to confirm the results obtained and improve the pigment selectivity. Conventional solvent extractions with tetrahydrofuran, dichloromethane or methanol, are the most described in literature. Nowadays, these solvents tend to be replaced by ethanol which is a more eco-friendly solvent and which showed promising results with a good pigment selectivity and a high extraction yield. Bio-based solvents such as edible oil, ionic liquids and natural deep eutectic solvents are also greatly considered as an ecological alternative for fucoxanthin extraction. The main challenge today is therefore to find the good balance between a high pigment selectivity for fucoxanthin, a high extraction yield, and a process that tends to fully respect the green chemistry principles. Following fucoxanthin extraction, purification processes can be performed. The most promising method seems to be the centrifugal partition chromatography, as this technique relies on a solvent system that can resemble to green solvents used for extraction. Furthermore, it requires a small amount of solvents, is fast, and has already resulted in fucoxanthin fractions purified at >99%.
Today, fucoxanthin is an emerging market specialized in pharmaceutical/nutraceutical with an increasing interest in the cosmetic industry. To our knowledge, no studies have demonstrated an interest in fucoxanthin for animal feeding (other than in aquaculture with the direct consumption of microalgae), nor as a coloring agent in a food or non-food. So far, there are only a few companies commercializing fucoxanthin. For both the pharmaceutical/nutraceutical and cosmetic markets, the products appear to be either a biomass extract of algae, or a purified fucoxanthin extract. In both cases, some products are also valued with the association of poly-unsaturated fatty acids.

Author Contributions

Conceptualization, A.P. and E.N.; investigation, A.P. and G.H.H.; writing—original draft preparation, A.P. and G.H.H.; writing—review and editing, L.P., L.M., and E.N.; visualization, A.P.; supervision, E.N.; project administration, E.N.; funding acquisition, E.N. and L.P. All authors have read and agreed to the published version of the manuscript.

Funding

The authors would like to acknowledge Ifremer and the Region Pays de la Loire (France) for the PhD grant of Anne Pajot, convention number 2020_03594. This work was co-funded by the Interreg Atlantic Area European regional development fund, project EnhanceMicroalgae EAPA_338/2016.

Institutional Review Board Statement

Not applicable.

Acknowledgments

The authors want to thank the Master Biorefinery of the University of Lille for the internship of Gia Hao Huynh.

Conflicts of Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to inappropriately influence the work reported in this paper.

References

  1. Liaaen-Jensen, S. Chapter 1—Marine Carotenoids. In Marine Natural Products; Scheuer, P.J., Ed.; Academic Press: Cambridge, MA, USA, 1978; pp. 1–73. ISBN 978-0-12-624002-3. [Google Scholar]
  2. D’Orazio, N.; Gemello, E.; Gammone, M.A.; De Girolamo, M.; Ficoneri, C.; Riccioni, G. Fucoxantin: A Treasure from the Sea. Mar. Drugs 2012, 10, 604–616. [Google Scholar] [CrossRef] [PubMed][Green Version]
  3. Wang, W.; Yu, L.-J.; Xu, C.; Tomizaki, T.; Zhao, S.; Umena, Y.; Chen, X.; Qin, X.; Xin, Y.; Suga, M.; et al. Structural basis for blue-green light harvesting and energy dissipation in diatoms. Science 2019, 363, eaav0365. [Google Scholar] [CrossRef] [PubMed]
  4. Junghans, A.; Sies, H.; Stahl, W. Macular Pigments Lutein and Zeaxanthin as Blue Light Filters Studied in Liposomes. Arch. Biochem. Biophys. 2001, 391, 160–164. [Google Scholar] [CrossRef] [PubMed]
  5. Kotake-Nara, E.; Terasaki, M.; Nagao, A. Characterization of Apoptosis Induced by Fucoxanthin in Human Promyelocytic Leukemia Cells. Biosci. Biotechnol. Biochem. 2005, 69, 224–227. [Google Scholar] [CrossRef]
  6. Paiva, S.A.R.; Russell, R.M. β-Carotene and Other Carotenoids as Antioxidants. J. Am. Coll. Nutr. 1999, 18, 426–433. [Google Scholar] [CrossRef]
  7. Englert, G.; Bjørnland, T.; Liaaen-Jensen, S. 1D and 2D NMR study of some allenic carotenoids of the fucoxanthin series. Org. Magn. Reson. 1990, 28, 519–528. [Google Scholar] [CrossRef]
  8. Peng, J.; Yuan, J.-P.; Wu, C.-F.; Wang, J.-H. Fucoxanthin, a Marine Carotenoid Present in Brown Seaweeds and Diatoms: Metabolism and Bioactivities Relevant to Human Health. Mar. Drugs 2011, 9, 1806–1828. [Google Scholar] [CrossRef]
  9. Sathasivam, R.; Ki, J.-S. A Review of the Biological Activities of Microalgal Carotenoids and Their Potential Use in Healthcare and Cosmetic Industries. Mar. Drugs 2018, 16, 26. [Google Scholar] [CrossRef][Green Version]
  10. Koo, S.Y.; Hwang, J.-H.; Yang, S.-H.; Um, J.-I.; Hong, K.W.; Kang, K.; Pan, C.-H.; Hwang, K.T.; Kim, S.M. Anti-Obesity Effect of Standardized Extract of Microalga Phaeodactylum tricornutum Containing Fucoxanthin. Mar. Drugs 2019, 17, 311. [Google Scholar] [CrossRef][Green Version]
  11. Kawee-Ai, A.; Kim, S.M. Application of Microalgal Fucoxanthin for the Reduction of Colon Cancer Risk: Inhibitory Activity of Fucoxanthin against β-Glucuronidase and DLD-1 Cancer Cells. NPC Nat. Prod. Commun. 2014, 5, 921–924. [Google Scholar]
  12. Liu, M.; Li, W.; Chen, Y.; Wan, X.; Wang, J. Fucoxanthin: A promising compound for human inflammation-related diseases. Life Sci. 2020, 255, 117850. [Google Scholar] [CrossRef] [PubMed]
  13. Zarekarizi, A.; Hoffmann, L.; Burritt, D. Approaches for the sustainable production of fucoxanthin, a xanthophyll with potential health benefits. J. Appl. Phycol. 2018, 31, 281–299. [Google Scholar] [CrossRef]
  14. Mordi, R.C. Mechanism of Beta-Carotene Degradation. Biochem. J. 1993, 292, 310–312. [Google Scholar] [CrossRef] [PubMed]
  15. Aman, R.; Schieber, A.; Carle, R. Effects of Heating and Illumination on Trans−Cis Isomerization and Degradation of β-Carotene and Lutein in Isolated Spinach Chloroplasts. J. Agric. Food Chem. 2005, 53, 9512–9518. [Google Scholar] [CrossRef] [PubMed]
  16. Achir, N.; Randrianatoandro, V.A.; Bohuon, P.; Laffargue, A.; Avallone, S. Kinetic study of β-carotene and lutein degradation in oils during heat treatment. Eur. J. Lipid Sci. Technol. 2010, 112, 349–361. [Google Scholar] [CrossRef]
  17. Rodriguez-Amaya, D.B. A Guide to Carotenoid Analysis in Foods; ILSI PRESS: Washington, DC, USA, 2001; 71p. [Google Scholar]
  18. Böhm, V.; Puspitasari-Nienaber, N.L.; Ferruzzi, M.G.; Schwartz, S.J. Trolox Equivalent Antioxidant Capacity of Different Geometrical Isomers of α-Carotene, β-Carotene, Lycopene, and Zeaxanthin. J. Agric. Food Chem. 2001, 50, 221–226. [Google Scholar] [CrossRef]
  19. Kawee-Ai, A.; Kuntiya, A.; Kim, S.M. Anticholinesterase and Antioxidant Activities of Fucoxanthin Purified from the Microalga Phaeodactylum Tricornutum. Nat. Prod. Commun. 2013, 8, 1381–1386. [Google Scholar] [CrossRef][Green Version]
  20. Zhang, Y.; Fang, H.; Xie, Q.; Sun, J.; Liu, R.; Hong, Z.; Yi, R.; Wu, H. Comparative Evaluation of the Radical-Scavenging Activities of Fucoxanthin and Its Stereoisomers. Molecules 2014, 19, 2100–2113. [Google Scholar] [CrossRef][Green Version]
  21. Nakazawa, Y.; Sashima, T.; Hosokawa, M.; Miyashita, K. Comparative evaluation of growth inhibitory effect of stereoisomers of fucoxanthin in human cancer cell lines. J. Funct. Foods 2009, 1, 88–97. [Google Scholar] [CrossRef]
  22. Premvardhan, L.; Bordes, L.; Beer, A.; Büchel, C.; Robert, B. Carotenoid Structures and Environments in Trimeric and Oligomeric Fucoxanthin Chlorophyll a/c2 Proteins from Resonance Raman Spectroscopy. J. Phys. Chem. B 2009, 113, 12565–12574. [Google Scholar] [CrossRef]
  23. Abu-Ghannam, N.; Shannon, E. Seaweed Carotenoid, Fucoxanthin, as Functional Food. In Microbial Functional Foods and Nutraceuticals; John Wiley & Sons, Ltd.: Hoboken, NJ, USA, 2017; pp. 39–64. ISBN 978-1-119-04896-1. [Google Scholar]
  24. Kuczynska, P.; Jemiola-Rzeminska, M.; Strzalka, K. Photosynthetic Pigments in Diatoms. Mar. Drugs 2015, 13, 5847–5881. [Google Scholar] [CrossRef] [PubMed]
  25. Rochaix, J.-D. Regulation and Dynamics of the Light-Harvesting System. Annu. Rev. Plant Biol. 2014, 65, 287–309. [Google Scholar] [CrossRef] [PubMed]
  26. Bauer, C.; Schmitz, C.; Corrêa, R.; Herrera, C.; Ramlov, F.; Oliveira, E.; Pizzato, A.; Varela, L.; Cabral, D.; Yunes, R.; et al. Chapter 8—In vitro fucoxanthin production by the Phaeodactylum tricornutum diatom. In Studies in Natural Products Chemistry; Elsevier: Amsterdam, The Netherlands, 2019; Volume 63, pp. 211–242. [Google Scholar] [CrossRef]
  27. Polívka, T.; Sundström, V. Ultrafast Dynamics of Carotenoid Excited States−From Solution to Natural and Artificial Systems. Chem. Rev. 2004, 104, 2021–2072. [Google Scholar] [CrossRef]
  28. Zigmantas, D.; Hiller, R.G.; Sharples, F.P.; Frank, H.A.; Sundström, V.; Polívka, T. Effect of a conjugated carbonyl group on the photophysical properties of carotenoids. Phys. Chem. Chem. Phys. 2004, 6, 3009–3016. [Google Scholar] [CrossRef]
  29. Premvardhan, L.; Sandberg, D.J.; Fey, H.; Birge, R.R.; Büchel, C.; van Grondelle, R. The Charge-Transfer Properties of the S2 State of Fucoxanthin in Solution and in Fucoxanthin Chlorophyll-a/c2 Protein (FCP) Based on Stark Spectroscopy and Molecular-Orbital Theory. J. Phys. Chem. B 2008, 112, 11838–11853. [Google Scholar] [CrossRef] [PubMed][Green Version]
  30. Gelzinis, A.; Butkus, V.; Songaila, E.; Augulis, R.; Gall, A.; Büchel, C.; Robert, B.; Abramavicius, D.; Zigmantas, D.; Valkunas, L. Mapping energy transfer channels in fucoxanthin–chlorophyll protein complex. Biochim. Biophys. Acta 2014, 1847, 241–247. [Google Scholar] [CrossRef]
  31. Polikva, T.; Zigmantas, D.; Hiller, R.G.; Sundström, V. Excited State Dynamics of the Carotenoid Peridinin. In Femtochemistry and Femtobiology: Ultrafast Events in Molecular Science; Martin, M.M., Hynes, J.T., Eds.; Elsevier: Amsterdam, The Netherlands, 2004; pp. 445–452. ISBN 978-0-08-050626-5. [Google Scholar]
  32. Di Valentin, M.; Büchel, C.; Giacometti, G.M.; Carbonera, D. Chlorophyll triplet quenching by fucoxanthin in the fucoxanthin–chlorophyll protein from the diatom Cyclotella meneghiniana. Biochem. Biophys. Res. Commun. 2012, 427, 637–641. [Google Scholar] [CrossRef]
  33. Nagao, R.; Yokono, M.; Akimoto, S.; Tomo, T. High Excitation Energy Quenching in Fucoxanthin Chlorophyll a/c-Binding Protein Complexes from the Diatom Chaetoceros gracilis. J. Phys. Chem. B 2013, 117, 6888–6895. [Google Scholar] [CrossRef]
  34. Goss, R.; Pinto, E.A.; Wilhelm, C.; Richter, M. The importance of a highly active and ΔpH-regulated diatoxanthin epoxidase for the regulation of the PS II antenna function in diadinoxanthin cycle containing algae. J. Plant Physiol. 2006, 163, 1008–1021. [Google Scholar] [CrossRef]
  35. Xiao, H.; Zhao, J.; Fang, C.; Cao, Q.; Xing, M.; Li, X.; Hou, J.; Ji, A.; Song, S. Advances in Studies on the Pharmacological Activities of Fucoxanthin. Mar. Drugs 2020, 18, 634. [Google Scholar] [CrossRef]
  36. Tiwari, A.; Melchor-Martínez, E.M.; Saxena, A.; Kapoor, N.; Singh, K.J.; Saldarriaga-Hernández, S.; Parra-Saldívar, R.; Iqbal, H.M. Therapeutic attributes and applied aspects of biological macromolecules (polypeptides, fucoxanthin, sterols, fatty acids, polysaccharides, and polyphenols) from diatoms—A review. Int. J. Biol. Macromol. 2021, 171, 398–413. [Google Scholar] [CrossRef] [PubMed]
  37. Aghajanpour, M.; Nazer, M.R.; Obeidavi, Z.; Akbari, M.; Ezati, P.; Kor, M. Functional Foods and Their Role in Cancer Pre-vention and Health Promotion: A Comprehensive Review. Am. J. Cancer Res. 2017, 30, 740–769. [Google Scholar]
  38. Irvani, N.; Hajiaghaee, R.; Zarekarizi, A.R. A Review on Biosynthesis, Health Benefits and Extraction Methods of Fucoxanthin, Particular Marine Carotenoids in Algae. J. Med. Plants 2018, 17, 25. [Google Scholar]
  39. Mohamadnia, S.; Tavakoli, O.; Faramarzi, M.A.; Shamsollahi, Z. Production of fucoxanthin by the microalga Tisochrysis lutea: A review of recent developments. Aquaculture 2019, 516, 734637. [Google Scholar] [CrossRef]
  40. Lourenço-Lopes, C.; Fraga-Corral, M.; Jimenez-Lopez, C.; Carpena, M.; Pereira, A.; Garcia-Oliveira, P.; Prieto, M.; Simal-Gandara, J. Biological action mechanisms of fucoxanthin extracted from algae for application in food and cosmetic industries. Trends Food Sci. Technol. 2021, 117, 163–181. [Google Scholar] [CrossRef]
  41. Wang, H.-M.D.; Chen, C.-C.; Huynh, P.; Chang, J.-S. Exploring the potential of using algae in cosmetics. Bioresour. Technol. 2014, 184, 355–362. [Google Scholar] [CrossRef]
  42. Khaw, Y.S.; Yusoff, F.M.; Tan, H.T.; Mazli, N.A.I.N.; Nazarudin, M.F.; Shaharuddin, N.A.; Omar, A.R. The Critical Studies of Fucoxanthin Research Trends from 1928 to June 2021: A Bibliometric Review. Mar. Drugs 2021, 19, 606. [Google Scholar] [CrossRef]
  43. Sugawara, T.; Baskaran, V.; Tsuzuki, W.; Nagao, A. Brown Algae Fucoxanthin Is Hydrolyzed to Fucoxanthinol during Absorption by Caco-2 Human Intestinal Cells and Mice. J. Nutr. 2002, 132, 946–951. [Google Scholar] [CrossRef][Green Version]
  44. Terasaki, M.; Takahashi, S.; Nishimura, R.; Kubota, A.; Kojima, H.; Ohta, T.; Hamada, J.; Kuramitsu, Y.; Maeda, H.; Miyashita, K.; et al. A Marine Carotenoid of Fucoxanthinol Accelerates the Growth of Human Pancreatic Cancer PANC-1 Cells. Nutr. Cancer 2021, 74, 357–371. [Google Scholar] [CrossRef]
  45. Terasaki, M.; Inoue, T.; Murase, W.; Kubota, A.; Kojima, H.; Kojoma, M.; Ohta, T.; Maeda, H.; Miyashita, K.; Mutoh, M.; et al. Fucoxanthinol Induces Apoptosis in a Pancreatic Intraepithelial Neoplasia Cell Line. Cancer Genom. Proteom. 2021, 18, 133–146. [Google Scholar] [CrossRef]
  46. Terasaki, M.; Nishizaka, Y.; Murase, W.; Kubota, A.; Kojima, H.; Kojoma, M.; Tanaka, T.; Maeda, H.; Miyashita, K.; Mutoh, M.; et al. Effect of Fucoxanthinol on Pancreatic Ductal Adenocarcinoma Cells from an N-Nitrosobis(2-oxopropyl)amine-initiated Syrian Golden Hamster Pancreatic Carcinogenesis Model. Cancer Genom. Proteom. 2021, 18 (Suppl. 3), 407–423. [Google Scholar] [CrossRef] [PubMed]
  47. Bigagli, E.; D’Ambrosio, M.; Cinci, L.; Niccolai, A.; Biondi, N.; Rodolfi, L.; Nascimiento, L.D.S.; Tredici, M.; Luceri, C. A Comparative In Vitro Evaluation of the Anti-Inflammatory Effects of a Tisochrysis lutea Extract and Fucoxanthin. Mar. Drugs 2021, 19, 334. [Google Scholar] [CrossRef]
  48. Matos, J.; Cardoso, C.; Gomes, A.; Campos, A.M.; Falé, P.; Afonso, C.; Bandarra, N.M. Bioprospection of Isochrysis galbanaand its potential as a nutraceutical. Food Funct. 2019, 10, 7333–7342. [Google Scholar] [CrossRef] [PubMed]
  49. Alghazwi, M.; Smid, S.; Musgrave, I.; Zhang, W. In vitro studies of the neuroprotective activities of astaxanthin and fucoxanthin against amyloid beta (Aβ1-42) toxicity and aggregation. Neurochem. Int. 2019, 124, 215–224. [Google Scholar] [CrossRef] [PubMed][Green Version]
  50. Molina, N.; Morandi, A.C.; Bolin, A.; Otton, R. Comparative effect of fucoxanthin and vitamin C on oxidative and functional parameters of human lymphocytes. Int. Immunopharmacol. 2014, 22, 41–50. [Google Scholar] [CrossRef]
  51. Zheng, J.; Piao, M.J.; Keum, Y.S.; Kim, H.S.; Hyun, J.W. Fucoxanthin Protects Cultured Human Keratinocytes against Oxidative Stress by Blocking Free Radicals and Inhibiting Apoptosis. Biomol. Ther. 2013, 21, 270–276. [Google Scholar] [CrossRef][Green Version]
  52. Terasaki, M.; Hamoya, T.; Kubota, A.; Kojima, H.; Tanaka, T.; Maeda, H.; Miyashita, K.; Mutoh, M. Fucoxanthin Prevents Colorectal Cancer Development in Dextran Sodium Sulfate-treated ApcMin/+ Mice. Anticancer Res. 2021, 41, 1299–1305. [Google Scholar] [CrossRef]
  53. Terasaki, M.; Uehara, O.; Ogasa, S.; Sano, T.; Kubota, A.; Kojima, H.; Tanaka, T.; Maeda, H.; Miyashita, K.; Mutoh, M. Alteration of fecal microbiota by fucoxanthin results in prevention of colorectal cancer in AOM/DSS mice. Carcinogenesis 2020, 42, 210–219. [Google Scholar] [CrossRef]
  54. Sui, Y.; Gu, Y.; Lu, Y.; Yu, C.; Zheng, J.; Qi, H. [email protected] Nanoparticles Promoted Oxidative Stress-Induced Cell Death in Caco-2 Human Colon Cancer Cells. Mar. Drugs 2021, 19, 92. [Google Scholar] [CrossRef]
  55. Yokoyama, R.; Kojima, H.; Takai, R.; Ohta, T.; Maeda, H.; Miyashita, K.; Mutoh, M.; Terasaki, M. Effects of CLIC4 on Fucoxanthinol-Induced Apoptosis in Human Colorectal Cancer Cells. Nutr. Cancer 2020, 73, 889–898. [Google Scholar] [CrossRef]
  56. Iyappan, P. Fucoxanthin induced apoptotic cell death in oral squamous carcinoma (KB) cells. Bioinformation 2021, 17, 181–191. [Google Scholar] [CrossRef] [PubMed]
  57. Pruteanu, L.-L.; Kopanitsa, L.; Módos, D.; Kletnieks, E.; Samarova, E.; Bender, A.; Gomez, L.D.; Bailey, D.S. Transcriptomics predicts compound synergy in drug and natural product treated glioblastoma cells. PLoS ONE 2020, 15, e0239551. [Google Scholar] [CrossRef] [PubMed]
  58. Ming, J.X.; Wang, Z.C.; Huang, Y.; Ohishi, H.; Wu, R.J.; Shao, Y.; Wang, H.; Qin, M.Y.; Wu, Z.L.; Li, Y.Y.; et al. Fucoxanthin extracted from Laminaria Japonica inhibits metastasis and enhances the sensitivity of lung cancer to Gefitinib. J. Ethnopharmacol. 2020, 265, 113302. [Google Scholar] [CrossRef] [PubMed]
  59. Nurcahyanti, A.D.R.; Kusmita, L.; Wink, M. Bixin and fucoxanthin sensitize human lung cancer and cervical cancer cell to cisplatin in vitro. BMC Res. Notes 2021, 14, 1–8. [Google Scholar] [CrossRef]
  60. Long, Y.; Cao, X.; Zhao, R.; Gong, S.; Jin, L.; Feng, C. Fucoxanthin treatment inhibits nasopharyngeal carcinoma cell proliferation through induction of autophagy mechanism. Environ. Toxicol. 2020, 35, 1082–1090. [Google Scholar] [CrossRef]
  61. Wu, S.-J.; Liou, C.-J.; Chen, Y.-L.; Cheng, S.-C.; Huang, W.-C. Fucoxanthin Ameliorates Oxidative Stress and Airway Inflammation in Tracheal Epithelial Cells and Asthmatic Mice. Cells 2021, 10, 1311. [Google Scholar] [CrossRef]
  62. Shih, P.-H.; Shiue, S.-J.; Chen, C.-N.; Cheng, S.-W.; Lin, H.-Y.; Wu, L.-W.; Wu, M.-S. Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD through Modulation of Leptin/Adiponectin Axis. Mar. Drugs 2021, 19, 148. [Google Scholar] [CrossRef]
  63. Takatani, N.; Kono, Y.; Beppu, F.; Okamatsu-Ogura, Y.; Yamano, Y.; Miyashita, K.; Hosokawa, M. Fucoxanthin inhibits hepatic oxidative stress, inflammation, and fibrosis in diet-induced nonalcoholic steatohepatitis model mice. Biochem. Biophys. Res. Commun. 2020, 528, 305–310. [Google Scholar] [CrossRef]
  64. Dai, Y.-L.; Jiang, Y.-F.; Lu, Y.-A.; Yu, J.-B.; Kang, M.-C.; Jeon, Y.-J. Fucoxanthin-rich fraction from Sargassum fusiformis alleviates particulate matter-induced inflammation in vitro and in vivo. Toxicol. Rep. 2021, 8, 349–358. [Google Scholar] [CrossRef]
  65. Takatani, N.; Taya, D.; Katsuki, A.; Beppu, F.; Yamano, Y.; Wada, A.; Miyashita, K.; Hosokawa, M. Identification of Paracentrone in Fucoxanthin-Fed Mice and Anti-Inflammatory Effect against Lipopolysaccharide-Stimulated Macrophages and Adipocytes. Mol. Nutr. Food Res. 2020, 65, e2000405. [Google Scholar] [CrossRef]
  66. Jin, W.; Yang, L.; Yi, Z.; Fang, H.; Chen, W.; Hong, Z.; Zhang, Y.; Zhang, G.; Li, L. Anti-Inflammatory Effects of Fucoxanthinol in LPS-Induced RAW264.7 Cells through the NAAA-PEA Pathway. Mar. Drugs 2020, 18, 222. [Google Scholar] [CrossRef] [PubMed][Green Version]
  67. Pang, Q.; Sun, G.; Xin, T.; Zhang, R.; Liu, C. Fucoxanthin attenuates behavior deficits and neuroinflammatory response in 1-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine-induced parkinson’s disease in mice. Pharmacogn. Mag. 2020, 16, 51. [Google Scholar] [CrossRef]
  68. Li, X.; Huang, R.; Liu, K.; Li, M.; Luo, H.; Cui, L.; Huang, L.; Luo, L. Fucoxanthin attenuates LPS-induced acute lung injury via inhibition of the TLR4/MyD88 signaling axis. Aging 2020, 13, 2655–2667. [Google Scholar] [CrossRef] [PubMed]
  69. Lykov, A.; Rachkovskaya, L.; Surovtseva, M.; Kim, I.; Gevorgiz, R.; Zheleznova, S.; Korolev, M.; Letyagin, A.; Poveshchenko, O. In Vitro and In Vivo Effect of the Composition of Fucoxanthin with Porous Aluminum-Silicon Career on Cells. Biointerface Res. Appl. Chem. 2021, 11, 9467–9476. [Google Scholar]
  70. Lee, A.-H.; Shin, H.-Y.; Park, J.-H.; Koo, S.Y.; Kim, S.M.; Yang, S.-H. Fucoxanthin from microalgae Phaeodactylum tricornutum inhibits pro-inflammatory cytokines by regulating both NF-κB and NLRP3 inflammasome activation. Sci. Rep. 2021, 11, 1–12. [Google Scholar] [CrossRef]
  71. Chen, S.-J.; Lin, T.-B.; Peng, H.-Y.; Lin, C.-H.; Lee, A.-S.; Liu, H.-J.; Li, C.-C.; Tseng, K.-W. Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species. Antioxidants 2021, 10, 1092. [Google Scholar] [CrossRef]
  72. Huang, L.L.; Huang, Z.Q.; Zhang, X.Q.; Liu, J.; Zhang, Y.P.; Zhao, H.Y.; Huang, M.Q. Effect of Fucoxanthin on Insulin Re-sistance in Obese Mice Induced by High Fat Diet. Zhongguo Zhong Yao Za Zhi 2021, 46, 171–176. [Google Scholar] [CrossRef]
  73. Du Preez, R.; Magnusson, M.; Majzoub, M.; Thomas, T.; Praeger, C.; Glasson, C.; Panchal, S.; Brown, L. Brown Seaweed Sargassum siliquosum as an Intervention for Diet-Induced Obesity in Male Wistar Rats. Nutrients 2021, 13, 1754. [Google Scholar] [CrossRef]
  74. Sun, X.; Zhao, H.; Liu, Z.; Sun, X.; Zhang, D.; Wang, S.; Xu, Y.; Zhang, G.; Wang, D. Modulation of Gut Microbiota by Fucoxanthin During Alleviation of Obesity in High-Fat Diet-Fed Mice. J. Agric. Food Chem. 2020, 68, 5118–5128. [Google Scholar] [CrossRef]
  75. Lu, Y.A.; Lee, H.G.; Li, X.; Hyun, J.-M.; Kim, H.-S.; Kim, T.H.; Kim, H.-M.; Lee, J.J.; Kang, M.-C.; Jeon, Y.-J. Anti-obesity effects of red seaweed, Plocamium telfairiae, in C57BL/6 mice fed a high-fat diet. Food Funct. 2020, 11, 2299–2308. [Google Scholar] [CrossRef]
  76. Oliyaei, N.; Moosavi-Nasab, M.; Tamaddon, A.M.; Tanideh, N. Antidiabetic effect of fucoxanthin extracted from Sargassum angustifolium on streptozotocin-nicotinamide-induced type 2 diabetic mice. Food Sci. Nutr. 2021, 9, 3521–3529. [Google Scholar] [CrossRef] [PubMed]
  77. Zhiyin, L.; Jinliang, C.; Qiunan, C.; Yunfei, Y.; Qian, X. Fucoxanthin rescues dexamethasone induced C2C12 myotubes atrophy. Biomed. Pharmacother. 2021, 139, 111590. [Google Scholar] [CrossRef] [PubMed]
  78. Yang, M.; Xuan, Z.; Wang, Q.; Yan, S.; Zhou, D.; Naman, C.B.; Zhang, J.; He, S.; Yan, X.; Cui, W. Fucoxanthin has potential for therapeutic efficacy in neurodegenerative disorders by acting on multiple targets. Nutr. Neurosci. 2021, 10, 1–14. [Google Scholar] [CrossRef] [PubMed]
  79. Wu, W.; Han, H.; Liu, J.; Tang, M.; Wu, X.; Cao, X.; Zhao, T.; Lu, Y.; Niu, T.; Chen, J.; et al. Fucoxanthin Prevents 6-OHDA-Induced Neurotoxicity by Targeting Keap1. Oxidative Med. Cell. Longev. 2021, 2021, 1–14. [Google Scholar] [CrossRef] [PubMed]
  80. Wei, J.; Mou, C.; Bao, Y.; Xie, Y.; Jin, H.; Shen, H.; Zhou, W.; Zhang, J.; He, S.; Chen, B.; et al. Fucoxanthin alleviates methamphetamine-induced neurotoxicity possibly via the inhibition of interaction between Keap1 and Nrf2. J. Funct. Foods 2021, 86, 104713. [Google Scholar] [CrossRef]
  81. Hudlikar, R.R.; Sargsyan, D.; Li, W.; Wu, R.; Zheng, M.; Kong, A.-N. Epigenomic, Transcriptomic, and Protective Effect of Carotenoid Fucoxanthin in High Glucose-Induced Oxidative Stress in Mes13 Kidney Mesangial Cells. Chem. Res. Toxicol. 2021, 34, 713–722. [Google Scholar] [CrossRef] [PubMed]
  82. El Bakary, N.M.; Thabet, N.M.; El Fatih, N.M.; Abdel-Rafei, M.K.; El Tawill, G.; Azab, K.S. Fucoxanthin alters the apelin-13/APJ pathway in certain organs of γ-irradiated mice. J. Radiat. Res. 2021, 62, 600–617. [Google Scholar] [CrossRef]
  83. Chiang, Y.-F.; Tsai, C.-H.; Chen, H.-Y.; Wang, K.-L.; Chang, H.-Y.; Huang, Y.-J.; Hong, Y.-H.; Ali, M.; Shieh, T.-M.; Huang, T.-C.; et al. Protective Effects of Fucoxanthin on Hydrogen Peroxide-Induced Calcification of Heart Valve Interstitial Cells. Mar. Drugs 2021, 19, 307. [Google Scholar] [CrossRef]
  84. Chen, S.-J.; Lin, T.-B.; Peng, H.-Y.; Liu, H.-J.; Lee, A.-S.; Lin, C.-H.; Tseng, K.-W. Cytoprotective Potential of Fucoxanthin in Oxidative Stress-Induced Age-Related Macular Degeneration and Retinal Pigment Epithelial Cell Senescence In Vivo and In Vitro. Mar. Drugs 2021, 19, 114. [Google Scholar] [CrossRef]
  85. Natsume, C.; Aoki, N.; Aoyama, T.; Senda, K.; Matsui, M.; Ikegami, A.; Tanaka, K.; Azuma, Y.-T.; Fujita, T. Fucoxanthin Ameliorates Atopic Dermatitis Symptoms by Regulating Keratinocytes and Regulatory Innate Lymphoid Cells. Int. J. Mol. Sci. 2020, 21, 2180. [Google Scholar] [CrossRef][Green Version]
  86. Guvatova, Z.; Dalina, A.; Marusich, E.; Pudova, E.; Snezhkina, A.; Krasnov, G.; Kudryavtseva, A.; Leonov, S.; Moskalev, A. Protective effects of carotenoid fucoxanthin in fibroblasts cellular senescence. Mech. Ageing Dev. 2020, 189, 111260. [Google Scholar] [CrossRef] [PubMed]
  87. Mao, H.; Wang, L.; Xiong, Y.; Jiang, G.; Liu, X. Fucoxanthin Attenuates Oxidative Damage by Activating the Sirt1/Nrf2/HO-1 Signaling Pathway to Protect the Kidney from Ischemia-Reperfusion Injury. Oxid. Med. Cell. Longev. 2022, 2022, 1–28. [Google Scholar] [CrossRef]
  88. Shi, Y.; Ren, J.; Zhao, B.; Zhu, T.; Qi, H. Photoprotective Mechanism of Fucoxanthin in Ultraviolet B Irradiation-Induced Retinal Müller Cells Based on Lipidomics Analysis. J. Agric. Food Chem. 2022, 70, 3181–3193. [Google Scholar] [CrossRef] [PubMed]
  89. Qiu, S.; Shen, Y.; Wu, Z.; Zhang, X.; Ge, S. Effects of algae subtype and extraction condition on extracted fucoxanthin antioxidant property: A 20-year meta-analysis. Algal Res. 2020, 53, 102161. [Google Scholar] [CrossRef]
  90. Mishra, B.; Tiwari, A. Cultivation of Anabena variabilis, Synechococcus elongatus, Spirulina platensis for the production of C-Phycocyanin, C-Phycoerythrin and Thalassiosira, Skeletonema, Chaetoceros for fucoxanthin. Syst. Microbiol. Biomanuf. 2021, 1, 356–361. [Google Scholar] [CrossRef]
  91. Karpiński, T.M.; Adamczak, A. Fucoxanthin—An Antibacterial Carotenoid. Antioxidants 2019, 8, 239. [Google Scholar] [CrossRef][Green Version]
  92. Karpiński, T.M.; Ożarowski, M.; Alam, R.; Łochyńska, M.; Stasiewicz, M. What Do We Know about Antimicrobial Activity of Astaxanthin and Fucoxanthin? Mar. Drugs 2021, 20, 36. [Google Scholar] [CrossRef]
  93. Yang, M.; Jin, L.; Wu, Z.; Xie, Y.; Zhang, P.; Wang, Q.; Yan, S.; Chen, B.; Liang, H.; Naman, C.B.; et al. PLGA-PEG Nanoparticles Facilitate In Vivo Anti-Alzheimer’s Effects of Fucoxanthin, a Marine Carotenoid Derived from Edible Brown Algae. J. Agric. Food Chem. 2021, 69, 9764–9777. [Google Scholar] [CrossRef]
  94. Ha, Y.-J.; Choi, Y.; Oh, Y.; Kang, E.; Khang, G.; Park, Y.-B.; Lee, Y. Fucoxanthin Suppresses Osteoclastogenesis via Modulation of MAP Kinase and Nrf2 Signaling. Mar. Drugs 2021, 19, 132. [Google Scholar] [CrossRef]
  95. Wang, R.; Younis, E.M.; Veeraraghavan, V.P.; Tian, C. Antiurolithiatic effect of Fucoxanthin on ethylene glycol-induced renal calculus in experimental rats. J. King Saud Univ.-Sci. 2020, 32, 1896–1901. [Google Scholar] [CrossRef]
  96. Li, Y.; Kim, M.-B.; Park, Y.-K.; Lee, J.-Y. Fucoxanthin metabolites exert anti-fibrogenic and antioxidant effects in hepatic stellate cells. J. Agric. Food Res. 2021, 6, 100245. [Google Scholar] [CrossRef]
  97. Takaichi, S. Carotenoids in Algae: Distributions, Biosyntheses and Functions. Mar. Drugs 2011, 9, 1101–1118. [Google Scholar] [CrossRef] [PubMed]
  98. Kwon, D.Y.; Vuong, T.T.; Choi, J.; Lee, T.S.; Um, J.-I.; Koo, S.Y.; Hwang, K.T.; Kim, S.M. Fucoxanthin biosynthesis has a positive correlation with the specific growth rate in the culture of microalga Phaeodactylum tricornutum. J. Appl. Phycol. 2021, 33, 1473–1485. [Google Scholar] [CrossRef]
  99. Gaidarenko, O.; Mills, D.W.; Vernet, M.; Hildebrand, M. Overexpression of Thalassiosira Pseudonana Violaxanthin de-Epoxidase-like 2 (VDL2) Increases Fucoxanthin While Stoichiometrically Reducing Diadinoxanthin Cycle Pigment Abundance. bioRxiv 2020. [Google Scholar] [CrossRef][Green Version]
  100. Lohr, M.; Wilhelm, C. Xanthophyll synthesis in diatoms: Quantification of putative intermediates and comparison of pigment conversion kinetics with rate constants derived from a model. Planta 2001, 212, 382–391. [Google Scholar] [CrossRef]
  101. Dautermann, O.; Lyska, D.; Andersen-Ranberg, J.; Becker, M.; Fröhlich-Nowoisky, J.; Gartmann, H.; Krämer, L.C.; Mayr, K.; Pieper, D.; Rij, L.M.; et al. An algal enzyme required for biosynthesis of the most abundant marine carotenoids. Sci. Adv. 2020, 6, eaaw9183. [Google Scholar] [CrossRef][Green Version]
  102. Beuzenberg, V.; Goodwin, E.O.; Puddick, J.; Romanazzi, D.; Adams, S.; Packer, M.A. Optimising conditions for growth and xanthophyll production in continuous culture of Tisochrysis lutea using photobioreactor arrays and central composite design experiments. N. Z. J. Bot. 2016, 55, 64–78. [Google Scholar] [CrossRef]
  103. De Oliveira-Júnior, R.G.; Grougnet, R.; Bodet, P.-E.; Bonnet, A.; Nicolau, E.; Jebali, A.; Rumin, J.; Picot, L. Updated pigment composition of Tisochrysis lutea and purification of fucoxanthin using centrifugal partition chromatography coupled to flash chromatography for the chemosensitization of melanoma cells. Algal Res. 2020, 51, 102035. [Google Scholar] [CrossRef]
  104. Hao, T.-B.; Lu, Y.; Zhang, Z.-H.; Liu, S.-F.; Wang, X.; Yang, W.-D.; Balamurugan, S.; Li, H.-Y. Hyperaccumulation of fucoxanthin by enhancing methylerythritol phosphate pathway in Phaeodactylum tricornutum. Appl. Microbiol. Biotechnol. 2021, 105, 8783–8793. [Google Scholar] [CrossRef]
  105. Handelman, G.J. The evolving role of carotenoids in human biochemistry. Nutrition 2001, 17, 818–822. [Google Scholar] [CrossRef]
  106. Zhang, H.; Tang, Y.; Zhang, Y.; Zhang, S.; Qu, J.; Wang, X.; Kong, R.; Han, C.; Liu, Z. Fucoxanthin: A Promising Medicinal and Nutritional Ingredient. Available online: https://www.hindawi.com/journals/ecam/2015/723515/ (accessed on 2 April 2020).
  107. Asai, A.; Sugawara, T.; Ono, H.; Nagao, A. Biotransformation of Fucoxanthinol into Amarouciaxanthin a in Mice and hepg2 Cells: Formation and Cytotoxicity of Fucoxanthin Metabolites. Drug Metab. Dispos. 2004, 32, 205–211. [Google Scholar] [CrossRef] [PubMed][Green Version]
  108. Hashimoto, T.; Ozaki, Y.; Taminato, M.; Das, S.K.; Mizuno, M.; Yoshimura, K.; Maoka, T.; Kanazawa, K. The distribution and accumulation of fucoxanthin and its metabolites after oral administration in mice. Br. J. Nutr. 2009, 102, 242–248. [Google Scholar] [CrossRef] [PubMed][Green Version]
  109. Petrushkina, M.; Gusev, E.; Sorokin, B.; Zotko, N.; Mamaeva, A.; Filimonova, A.; Kulikovskiy, M.; Maltsev, Y.; Yampolsky, I.; Guglya, E.; et al. Fucoxanthin production by heterokont microalgae. Algal Res. 2017, 24, 387–393. [Google Scholar] [CrossRef]
  110. McClure, D.D.; Luiz, A.; Gerber, B.; Barton, G.W.; Kavanagh, J.M. An investigation into the effect of culture conditions on fucoxanthin production using the marine microalgae Phaeodactylum tricornutum. Algal Res. 2018, 29, 41–48. [Google Scholar] [CrossRef]
  111. Mohamadnia, S.; Tavakoli, O.; Faramarzi, M.A. Enhancing production of fucoxanthin by the optimization of culture media of the microalga Tisochrysis lutea. Aquaculture 2020, 533, 736074. [Google Scholar] [CrossRef]
  112. Gao, F.; Cabanelas, I.T.D.; Wijffels, R.H.; Barbosa, M.J. Fucoxanthin and docosahexaenoic acid production by cold-adapted Tisochrysis lutea. New Biotechnol. 2021, 66, 16–24. [Google Scholar] [CrossRef]
  113. Gao, F.; Sá, M.; Cabanelas, I.T.D.; Wijffels, R.H.; Barbosa, M.J. Improved fucoxanthin and docosahexaenoic acid productivities of a sorted self-settling Tisochrysis lutea phenotype at pilot scale. Bioresour. Technol. 2021, 325, 124725. [Google Scholar] [CrossRef]
  114. Gao, F.; Cabanelas, I.I.T.; Wijffels, R.H.; Barbosa, M.J. Process optimization of fucoxanthin production with Tisochrysis lutea. Bioresour. Technol. 2020, 315, 123894. [Google Scholar] [CrossRef]
  115. Gao, F.; Cabanelas, I.I.T.; Ferrer-Ledo, N.; Wijffels, R.H.; Barbosa, M.J. Production and high throughput quantification of fucoxanthin and lipids in Tisochrysis lutea using single-cell fluorescence. Bioresour. Technol. 2020, 318, 124104. [Google Scholar] [CrossRef]
  116. Gao, F.; Woolschot, S.; Cabanelas, I.T.D.; Wijffels, R.H.; Barbosa, M.J. Light spectra as triggers for sorting improved strains of Tisochrysis lutea. Bioresour. Technol. 2020, 321, 124434. [Google Scholar] [CrossRef]
  117. Gao, F.; Sá, M.; Cabanelas, I.I.T.; Wijffels, R.H.; Barbosa, M.J. Production and monitoring of biomass and fucoxanthin with brown microalgae under outdoor conditions. Biotechnol. Bioeng. 2020, 118, 1355–1365. [Google Scholar] [CrossRef] [PubMed]
  118. Pereira, H.; Sá, M.; Maia, I.; Rodrigues, A.; Teles, I.; Wijffels, R.H.; Navalho, J.; Barbosa, M. Fucoxanthin production from Tisochrysis lutea and Phaeodactylum tricornutum at industrial scale. Algal Res. 2021, 56, 102322. [Google Scholar] [CrossRef]
  119. Kanamoto, A.; Kato, Y.; Yoshida, E.; Hasunuma, T.; Kondo, A. Development of a Method for Fucoxanthin Production Using the Haptophyte Marine Microalga Pavlova sp. OPMS 30543. Mar. Biotechnol. 2021, 23, 331–341. [Google Scholar] [CrossRef]
  120. Li, Y.; Sun, H.; Wang, Y.; Yang, S.; Wang, J.; Wu, T.; Lu, X.; Chu, Y.; Chen, F. Integrated metabolic tools reveal carbon alternative in Isochrysis zhangjiangensis for fucoxanthin improvement. Bioresour. Technol. 2021, 347, 126401. [Google Scholar] [CrossRef] [PubMed]
  121. Yang, R.; Wei, D. Improving Fucoxanthin Production in Mixotrophic Culture of Marine Diatom Phaeodactylum tricornutum by LED Light Shift and Nitrogen Supplementation. Front. Bioeng. Biotechnol. 2020, 8, 820. [Google Scholar] [CrossRef] [PubMed]
  122. Derwenskus, F.; Weickert, S.; Lewandowski, I.; Schmid-Staiger, U.; Hirth, T. Economic evaluation of up- and downstream scenarios for the co-production of fucoxanthin and eicosapentaenoic acid with P. tricornutum using flat-panel airlift photobioreactors with artificial light. Algal Res. 2020, 51, 102078. [Google Scholar] [CrossRef]
  123. Wang, Z.-P.; Wang, P.-K.; Ma, Y.; Lin, J.-X.; Wang, C.-L.; Zhao, Y.-X.; Zhang, X.-Y.; Huang, B.-C.; Zhao, S.-G.; Gao, L.; et al. Laminaria japonica hydrolysate promotes fucoxanthin accumulation in Phaeodactylum tricornutum. Bioresour. Technol. 2021, 344, 126117. [Google Scholar] [CrossRef]
  124. Bárcenas-Pérez, D.; Střížek, A.; Hrouzek, P.; Kopecký, J.; Barradas, M.; Sierra-Ramirez, A.; Fernandez-Marcos, P.J.; Cheel, J. Production of Fucoxanthin from Phaeodactylum tricornutum Using High Performance Countercurrent Chromatography Retaining Its FOXO3 Nuclear Translocation-Inducing Effect. Mar. Drugs 2021, 19, 517. [Google Scholar] [CrossRef]
  125. Rehmanji, M.; Nesamma, A.; Khan, N.; Fatma, T.; Jutur, P. Media Engineering in Marine Diatom Phaeodactylum Tricornutum Employing Cost-Effective Substrates for Sustainable Production of High Value Renewables. Authorea 2022. [Google Scholar] [CrossRef]
  126. Jiang, J.; Huang, J.; Zhang, H.; Zhang, Z.; Du, Y.; Cheng, Z.; Feng, B.; Yao, T.; Zhang, A.; Zhao, Z. Potential integration of wastewater treatment and natural pigment production by Phaeodactylum tricornutum: Microalgal growth, nutrient removal, and fucoxanthin accumulation. J. Appl. Phycol. 2022, 1–12. [Google Scholar] [CrossRef]
  127. Khoo, K.S.; Ooi, C.W.; Chew, K.W.; Foo, S.C.; Show, P.L. Bioprocessing of Chaetoceros calcitrans for the recovery of fucoxanthin using CO2-based alkyl carbamate ionic liquids. Bioresour. Technol. 2020, 322, 124520. [Google Scholar] [CrossRef] [PubMed]
  128. Mc Gee, D.; Archer, L.; Fleming, G.T.; Gillespie, E.; Touzet, N. The effect of nutrient and phytohormone supplementation on the growth, pigment yields and biochemical composition of newly isolated microalgae. Process Biochem. 2020, 92, 61–68. [Google Scholar] [CrossRef]
  129. Parkes, R.; Archer, L.; Mc Gee, D.; Smyth, T.J.; Gillespie, E.; Touzet, N. Differential responses in EPA and fucoxanthin production by the marine diatom Stauroneis sp. under varying cultivation conditions. Biotechnol. Prog. 2021, 37, e3197. [Google Scholar] [CrossRef] [PubMed]
  130. Marella, T.K.; Tiwari, A. Marine diatom Thalassiosira weissflogii based biorefinery for co-production of eicosapentaenoic acid and fucoxanthin. Bioresour. Technol. 2020, 307, 123245. [Google Scholar] [CrossRef] [PubMed]
  131. Zhang, H.; Gong, P.; Cai, Q.; Zhang, C.; Gao, B. Maximizing fucoxanthin production in Odontella aurita by optimizing the ratio of red and blue light-emitting diodes in an auto-controlled internally illuminated photobioreactor. Bioresour. Technol. 2021, 344, 126260. [Google Scholar] [CrossRef] [PubMed]
  132. Erdoğan, A.; Karataş, A.B.; Demirel, Z.; Dalay, M.C. Purification of fucoxanthin from the diatom Amphora capitellata by preparative chromatography after its enhanced productivity via oxidative stress. J. Appl. Phycol. 2021, 34, 301–309. [Google Scholar] [CrossRef]
  133. Mao, X.; Chen, S.H.Y.; Lu, X.; Yu, J.; Liu, B. High silicate concentration facilitates fucoxanthin and eicosapentaenoic acid (EPA) production under heterotrophic condition in the marine diatom Nitzschia laevis. Algal Res. 2020, 52, 102086. [Google Scholar] [CrossRef]
  134. Couto, C.; Hernández, C.P.; Sobrinho, R.C.M.A.; Mendes, C.R.B.; Roselet, F.; Abreu, P.C. Optimization of a low-cost fertilizer-based medium for large-scale cultivation of the coastal diatom Conticribra weissflogii using response surface methodology and its effects on biomass composition. J. Appl. Phycol. 2021, 33, 2767–2781. [Google Scholar] [CrossRef]
  135. Gérin, S.; Delhez, T.; Corato, A.; Remacle, C.; Franck, F. A novel culture medium for freshwater diatoms promotes efficient photoautotrophic batch production of biomass, fucoxanthin, and eicosapentaenoic acid. J. Appl. Phycol. 2020, 32, 1581–1596. [Google Scholar] [CrossRef]
  136. Tachihana, S.; Nagao, N.; Katayama, T.; Hirahara, M.; Yusoff, F.M.; Banerjee, S.; Shariff, M.; Kurosawa, N.; Toda, T.; Furuya, K. High Productivity of Eicosapentaenoic Acid and Fucoxanthin by a Marine Diatom Chaetoceros gracilis in a Semi-Continuous Culture. Front. Bioeng. Biotechnol. 2020, 8, 602721. [Google Scholar] [CrossRef]
  137. Boeing, P. Larval Feed Alternatives. Glob. Aquac. Advocate 1999, 3, 48–50. [Google Scholar]
  138. Aghzar, A.; Miñambres, M.; Alvarez, P.; Presa, P. A Cost-Benefit Assessment of Two Multi-Species Algae Diets for Juveniles of Mytilus Galloprovincialis. Thalassas 2013, 29, 9–16. [Google Scholar]
  139. Fernandez, F.G.A.; Hall, D.O.; Guerrero, E.C.; Rao, K.K.; Grima, E.M. Outdoor production of Phaeodactylum tricornutum biomass in a helical reactor. J. Biotechnol. 2003, 103, 137–152. [Google Scholar] [CrossRef]
  140. Kim, S.M.; Kang, S.-W.; Kwon, O.-N.; Chung, D.; Pan, C.-H. Fucoxanthin as a major carotenoid in Isochrysis aff. galbana: Characterization of extraction for commercial application. J. Korean Soc. Appl. Biol. Chem. 2012, 55, 477–483. [Google Scholar] [CrossRef]
  141. Sun, Z.; Wang, X.; Liu, J. Screening of Isochrysis strains for simultaneous production of docosahexaenoic acid and fucoxanthin. Algal Res. 2019, 41, 101545. [Google Scholar] [CrossRef]
  142. Leal, E.; de Beyer, L.; O’Connor, W.; Dove, M.; Ralph, P.J.; Pernice, M. Production optimisation of Tisochrysis lutea as a live feed for juvenile Sydney rock oysters, Saccostrea glomerata, using large-scale photobioreactors. Aquaculture 2020, 533, 736077. [Google Scholar] [CrossRef]
  143. Rico-Villa, B.; Le Coz, J.; Mingant, C.; Robert, R. Influence of phytoplankton diet mixtures on microalgae consumption, larval development and settlement of the Pacific oyster Crassostrea gigas (Thunberg). Aquaculture 2006, 256, 377–388. [Google Scholar] [CrossRef][Green Version]
  144. Custódio, L.; Soares, F.; Pereira, H.; Barreira, L.; Vizetto-Duarte, C.; Rodrigues, M.J.; Rauter, A.P.; Alberício, F.; Varela, J. Fatty acid composition and biological activities of Isochrysis galbana T-ISO, Tetraselmis sp. and Scenedesmus sp.: Possible application in the pharmaceutical and functional food industries. J. Appl. Phycol. 2013, 26, 151–161. [Google Scholar] [CrossRef]
  145. Delbrut, A.; Albina, P.; Lapierre, T.; Pradelles, R.; Dubreucq, E. Fucoxanthin and Polyunsaturated Fatty Acids Co-Extraction by a Green Process. Molecules 2018, 23, 874. [Google Scholar] [CrossRef][Green Version]
  146. Alkhamis, Y.; Qin, J.G. Comparison of pigment and proximate compositions of Tisochrysis lutea in phototrophic and mixotrophic cultures. J. Appl. Phycol. 2015, 28, 35–42. [Google Scholar] [CrossRef]
  147. Chen, G.; Chen, F. Growing Phototrophic Cells without Light. Biotechnol. Lett. 2006, 28, 607–616. [Google Scholar] [CrossRef] [PubMed]
  148. Saoudi-Helis, L.; Dubacq, J.P.; Marty, Y.; Samain, J.F.; Gudin, C. Influence of growth rate on pigment and lipid composition of the microalga Isochrysis aff.galbana clone T.iso. J. Appl. Phycol. 1994, 6, 315–322. [Google Scholar] [CrossRef]
  149. Fret, J.; Roef, L.; Diels, L.; Tavernier, S.; Vyverman, W.; Michiels, M. Combining medium recirculation with alternating the microalga production strain: A laboratory and pilot scale cultivation test. Algal Res. 2020, 46, 101763. [Google Scholar] [CrossRef]
  150. Ardiles, P.; Cerezal-Mezquita, P.; Salinas-Fuentes, F.; Órdenes, D.; Renato, G.; Ruiz-Domínguez, M.C. Biochemical Composition and Phycoerythrin Extraction from Red Microalgae: A Comparative Study Using Green Extraction Technologies. Processes 2020, 8, 1628. [Google Scholar] [CrossRef]
  151. Medipally, S.R.; Yusoff, F.M.; Banerjee, S.; Shariff, M. Microalgae as Sustainable Renewable Energy Feedstock for Biofuel Production. BioMed Res. Int. 2015, 2015, 1–13. [Google Scholar] [CrossRef]
  152. Ishika, T.; Moheimani, N.R.; Bahri, P.A.; Laird, D.W.; Blair, S.; Parlevliet, D. Halo-adapted microalgae for fucoxanthin production: Effect of incremental increase in salinity. Algal Res. 2017, 28, 66–73. [Google Scholar] [CrossRef]
  153. Torzillo, G.; Faraloni, C.; Silva, A.M.; Kopecký, J.; Pilný, J.; Masojidek, J. Photoacclimation of Phaeodactylum tricornutum (Bacillariophyceae) cultures grown outdoors in photobioreactors and open ponds. Eur. J. Phycol. 2012, 47, 169–181. [Google Scholar] [CrossRef]
  154. Leong, Y.K.; Chen, C.-Y.; Varjani, S.; Chang, J.-S. Producing fucoxanthin from algae—Recent advances in cultivation strategies and downstream processing. Bioresour. Technol. 2021, 344, 126170. [Google Scholar] [CrossRef]
  155. Xia, S.; Wang, K.; Wan, L.; Li, A.; Hu, Q.; Zhang, C. Production, Characterization, and Antioxidant Activity of Fucoxanthin from the Marine Diatom Odontella aurita. Mar. Drugs 2013, 11, 2667–2681. [Google Scholar] [CrossRef]
  156. Kavadikeri, S.; Manokaran, S.; Reddy, A.H.M. Extraction and Characterization of Microalgal Oil and Fucoxanthin from Diatom. J. Pharm. Sci. 2020, 12, 5. [Google Scholar]
  157. Guler, B.A.; Deniz, I.; Demirel, Z.; Oncel, S.S.; Imamoglu, E. Transition from start-up to scale-up for fucoxanthin production in flat plate photobioreactor. J. Appl. Phycol. 2019, 31, 1525–1533. [Google Scholar] [CrossRef]
  158. Gao, B.; Chen, A.; Zhang, W.; Li, A.; Zhang, C. Co-production of lipids, eicosapentaenoic acid, fucoxanthin, and chrysolaminarin by Phaeodactylum tricornutum cultured in a flat-plate photobioreactor under varying nitrogen conditions. J. Ocean Univ. China 2017, 16, 916–924. [Google Scholar] [CrossRef]
  159. Guler, B.A.; Deniz, I.; Demirel, Z.; Oncel, S.S.; Imamoglu, E. Comparison of different photobioreactor configurations and empirical computational fluid dynamics simulation for fucoxanthin production. Algal Res. 2018, 37, 195–204. [Google Scholar] [CrossRef]
  160. Wang, H.; Zhang, Y.; Chen, L.; Cheng, W.; Liu, T. Combined production of fucoxanthin and EPA from two diatom strains Phaeodactylum tricornutum and Cylindrotheca fusiformis cultures. Bioprocess Biosyst. Eng. 2018, 41, 1061–1071. [Google Scholar] [CrossRef]
  161. Lu, X.; Sun, H.; Zhao, W.; Cheng, K.-W.; Chen, F.; Liu, B. A Hetero-Photoautotrophic Two-Stage Cultivation Process for Production of Fucoxanthin by the Marine Diatom Nitzschia laevis. Mar. Drugs 2018, 16, 219. [Google Scholar] [CrossRef] [PubMed][Green Version]
  162. Wu, S.; Xie, X.; Huan, L.; Zheng, Z.; Zhao, P.; Kuang, J.; Liu, X.; Wang, G. Selection of optimal flocculant for effective harvesting of the fucoxanthin-rich marine microalga Isochrysis galbana. J. Appl. Phycol. 2015, 28, 1579–1588. [Google Scholar] [CrossRef]
  163. Fitt, W.K.; Dunne, R.P.; Gibb, S.; Cummings, D.G.; Ambarsari, I.; Brown, B.E.; Warner, M.E. Diurnal changes in photochemical efficiency and xanthophyll concentrations in shallow water reef corals: Evidence for photoinhibition and photoprotection. Coral Reefs 1999, 18, 99–105. [Google Scholar] [CrossRef]
  164. Anning, T.; MacIntyre, H.L.; Pratt, S.M.; Sammes, P.J.; Gibb, S.; Geider, R.J. Photoacclimation in the marine diatom Skeletonema costatum. Limnol. Oceanogr. 2000, 45, 1807–1817. [Google Scholar] [CrossRef]
  165. Lavaud, J.; Rousseau, B.; van Gorkom, H.J.; Etienne, A.-L. Influence of the Diadinoxanthin Pool Size on Photoprotection in the Marine Planktonic Diatom Phaeodactylum tricornutum. Plant Physiol. 2002, 129, 1398–1406. [Google Scholar] [CrossRef][Green Version]
  166. Demmig-Adams, B.; Garab, G.; Adams, W.W. Govindjee Non-Photochemical Quenching and Energy Dissipation in Plants, Algae and Cyanobacteria; Advances in Photosynthesis and Respiration; Springer: Dordrecht, The Netherlands, 2014; Volume 40, ISBN 978-94-017-9031-4. [Google Scholar]
  167. Zigman, M.; Dubinsky, Z.; Iluz, D. The Xanthophyll Cycle in Aquatic Phototrophs and Its Role in the Mitigation of Photoin-hibition and Photodynamic Damage. In Applied Photosynthesis; Najafpour, M., Ed.; InTech: London, UK, 2012; ISBN 978-953-51-0061-4. [Google Scholar]
  168. Zhao, D.; Kim, S.-M.; Pan, C.-H.; Chung, D. Effects of heating, aerial exposure and illumination on stability of fucoxanthin in canola oil. Food Chem. 2014, 145, 505–513. [Google Scholar] [CrossRef]
  169. Guo, B.; Liu, B.; Yang, B.; Sun, P.; Lu, X.; Liu, J.; Chen, F. Screening of Diatom Strains and Characterization of Cyclotella cryptica as A Potential Fucoxanthin Producer. Mar. Drugs 2016, 14, 125. [Google Scholar] [CrossRef] [PubMed][Green Version]
  170. Goss, R.; Jakob, T. Regulation and function of xanthophyll cycle-dependent photoprotection in algae. Photosynth. Res. 2010, 106, 103–122. [Google Scholar] [CrossRef] [PubMed]
  171. Harris, G.N.; Scanlan, D.J.; Geider, R.J. Responses of Emiliania huxleyi (Prymnesiophyceae) to step changes in photon flux density. Eur. J. Phycol. 2009, 44, 31–48. [Google Scholar] [CrossRef][Green Version]
  172. Muüller, P.; Li, X.-P.; Niyogi, K.K. Non-Photochemical Quenching. A Response to Excess Light Energy. Plant Physiol. 2001, 125, 1558–1566. [Google Scholar] [CrossRef][Green Version]
  173. Wang, S.; Verma, S.K.; Said, I.H.; Thomsen, L.; Ullrich, M.S.; Kuhnert, N. Changes in the fucoxanthin production and protein profiles in Cylindrotheca closterium in response to blue light-emitting diode light. Microb. Cell Factories 2018, 17, 110. [Google Scholar] [CrossRef]
  174. Wright, S.; Jeffrey, S. Fucoxanthin pigment markers of marine phytoplankton analysed by HPLC and HPTLC. Mar. Ecol. Prog. Ser. 1987, 38, 259–266. [Google Scholar] [CrossRef]
  175. Geider, R.; La Roche, J. Redfield revisited: Variability of C:N:P in marine microalgae and its biochemical basis. Eur. J. Phycol. 2002, 37, 1–17. [Google Scholar] [CrossRef][Green Version]
  176. Gómez, A.; Benavides, J.; Rito-Palomares, M. Growth kinetics and fucoxanthin production of Phaeodactylum tricornutum and Isochrysis galbana cultures at different light and agitation conditions. J. Appl. Phycol. 2015, 28, 849–860. [Google Scholar] [CrossRef]
  177. Gupta, P.; Lee, S.-M.; Choi, H.-J. Integration of microalgal cultivation system for wastewater remediation and sustainable biomass production. World J. Microbiol. Biotechnol. 2016, 32, 139. [Google Scholar] [CrossRef]
  178. Flynn, K.; Fasham, M.J.R.; Hipkin, C.R. Modelling the interactions between ammonium and nitrate uptake in marine phytoplankton. Philos. Trans. R. Soc. B Biol. Sci. 1997, 352, 1625–1645. [Google Scholar] [CrossRef]
  179. Bhaya, D.; Schwarz, R.; Grossman, A.R. Molecular Responses to Environmental Stress. In The Ecology of Cyanobacteria; Whitton, B.A., Potts, M., Eds.; Springer: Dordrecht, The Netherlands, 2006; pp. 397–442. [Google Scholar] [CrossRef]
  180. Fuggi, A.; Rigano, V.D.M.; Vona, V.; Rigano, C. Nitrate and ammonium assimilation in algal cell-suspensions and related pH variations in the external medium, monitored by electrodes. Plant Sci. Lett. 1981, 23, 129–138. [Google Scholar] [CrossRef]
  181. Mairet, F.; Bernard, O.; Lacour, T.; Sciandra, A. Modelling microalgae growth in nitrogen limited photobiorector for estimating biomass, carbohydrate and neutral lipid productivities. IFAC Proc. Vol. 2011, 44, 10591–10596. [Google Scholar] [CrossRef][Green Version]
  182. Bougaran, G.; Bernard, O.; Sciandra, A. Modeling continuous cultures of microalgae colimited by nitrogen and phosphorus. J. Theor. Biol. 2010, 265, 443–454. [Google Scholar] [CrossRef][Green Version]
  183. Costa, S.S.; Miranda, A.L.; Andrade, B.B.; Assis, D.; de Souza, C.O.; de Morais, M.G.; Costa, J.A.V.; Druzian, J.I. Influence of nitrogen on growth, biomass composition, production, and properties of polyhydroxyalkanoates (PHAs) by microalgae. Int. J. Biol. Macromol. 2018, 116, 552–562. [Google Scholar] [CrossRef]
  184. Zarrinmehr, M.J.; Farhadian, O.; Heyrati, F.P.; Keramat, J.; Koutra, E.; Kornaros, M.; Daneshvar, E. Effect of nitrogen concentration on the growth rate and biochemical composition of the microalga, Isochrysis galbana. Egypt. J. Aquat. Res. 2019, 46, 153–158. [Google Scholar] [CrossRef]
  185. Moussa, I.D.-B.; Chtourou, H.; Karray, F.; Sayadi, S.; Dhouib, A. Nitrogen or phosphorus repletion strategies for enhancing lipid or carotenoid production from Tetraselmis marina. Bioresour. Technol. 2017, 238, 325–332. [Google Scholar] [CrossRef]
  186. Geider, R.; Intyre, M.; Graziano, L.; McKay, R. Responses of the photosynthetic apparatus of Dunaliella tertiolecta (Chlorophyceae) to nitrogen and phosphorus limitation. Eur. J. Phycol. 1998, 33, 315–332. [Google Scholar] [CrossRef]
  187. De Wever, A.; Muylaert, K.; Langlet, D.; Alleman, L.; Descy, J.-P.; André, L.; Cocquyt, C.; Vyverman, W. Differential response of phytoplankton to additions of nitrogen, phosphorus and iron in Lake Tanganyika. Freshw. Biol. 2007, 53, 264–277. [Google Scholar] [CrossRef]
  188. Xia, S.; Gao, B.; Fu, J.; Xiong, J.; Zhang, C. Production of fucoxanthin, chrysolaminarin, and eicosapentaenoic acid by Odontella aurita under different nitrogen supply regimes. J. Biosci. Bioeng. 2018, 126, 723–729. [Google Scholar] [CrossRef]
  189. Sahin, M.S.; Khazi, M.I.; Demirel, Z.; Dalay, M.C. Variation in growth, fucoxanthin, fatty acids profile and lipid content of marine diatoms Nitzschia sp. and Nanofrustulum shiloi in response to nitrogen and iron. Biocatal. Agric. Biotechnol. 2019, 17, 390–398. [Google Scholar] [CrossRef]
  190. Novoveská, L.; Ross, M.E.; Stanley, M.S.; Pradelles, R.; Wasiolek, V.; Sassi, J.-F. Microalgal Carotenoids: A Review of Production, Current Markets, Regulations, and Future Direction. Mar. Drugs 2019, 17, 640. [Google Scholar] [CrossRef] [PubMed][Green Version]
  191. Yi, Z.; Su, Y.; Cherek, P.; Nelson, D.R.; Lin, J.; Rolfsson, O.; Wu, H.; Salehi-Ashtiani, K.; Brynjolfsson, S.; Fu, W. Combined artificial high-silicate medium and LED illumination promote carotenoid accumulation in the marine diatom Phaeodactylum tricornutum. Microb. Cell Factories 2019, 18, 1–11. [Google Scholar] [CrossRef] [PubMed]
  192. Pal, P.; Chew, K.W.; Yen, H.-W.; Lim, J.W.; Lam, M.K.; Show, P.L. Cultivation of Oily Microalgae for the Production of Third-Generation Biofuels. Sustainability 2019, 11, 5424. [Google Scholar] [CrossRef][Green Version]
  193. Moreno-García, L.; Adjallé, K.; Barnabé, S.; Raghavan, G.S.V. Microalgae biomass production for a biorefinery system: Recent advances and the way towards sustainability. Renew. Sustain. Energy Rev. 2017, 76, 493–506. [Google Scholar] [CrossRef]
  194. Lu, X.; Liu, B.; He, Y.; Guo, B.; Sun, H.; Chen, F. Novel insights into mixotrophic cultivation of Nitzschia laevis for co-production of fucoxanthin and eicosapentaenoic acid. Bioresour. Technol. 2019, 294, 122145. [Google Scholar] [CrossRef]
  195. Patel, A.; Matsakas, L.; Hrůzová, K.; Rova, U.; Christakopoulos, P. Biosynthesis of Nutraceutical Fatty Acids by the Oleaginous Marine Microalgae Phaeodactylum tricornutum Utilizing Hydrolysates from Organosolv-Pretreated Birch and Spruce Biomass. Mar. Drugs 2019, 17, 119. [Google Scholar] [CrossRef] [PubMed][Green Version]
  196. García, M.C.; Mirón, A.S.; Sevilla, J.M.F.; Grima, E.M.; Garcia-Camacho, F. Mixotrophic growth of the microalga Phaeodactylum tricornutum: Influence of different nitrogen and organic carbon sources on productivity and biomass composition. Process Biochem. 2005, 40, 297–305. [Google Scholar] [CrossRef]
  197. Cerón-García, M.; Fernández-Sevilla, J.; Sánchez-Mirón, A.; García-Camacho, F.; Contreras-Gómez, A.; Molina-Grima, E. Mixotrophic growth of Phaeodactylum tricornutum on fructose and glycerol in fed-batch and semi-continuous modes. Bioresour. Technol. 2013, 147, 569–576. [Google Scholar] [CrossRef]
  198. Kim, S.M.; Jung, Y.-J.; Kwon, O.-N.; Cha, K.H.; Um, B.-H.; Chung, D.; Pan, C.-H. A Potential Commercial Source of Fucoxanthin Extracted from the Microalga Phaeodactylum tricornutum. Appl. Biochem. Biotechnol. 2012, 166, 1843–1855. [Google Scholar] [CrossRef]
  199. Miyashita, K.; Beppu, F.; Hosokawa, M.; Liu, X.; Wang, S. Bioactive significance of fucoxanthin and its effective extraction. Biocatal. Agric. Biotechnol. 2020, 26, 101639. [Google Scholar] [CrossRef]
  200. Zhang, W.; Wang, F.; Gao, B.; Huang, L.; Zhang, C. An integrated biorefinery process: Stepwise extraction of fucoxanthin, eicosapentaenoic acid and chrysolaminarin from the same Phaeodactylum tricornutum biomass. Algal Res. 2018, 32, 193–200. [Google Scholar] [CrossRef]
  201. Kapoore, R.V.; Butler, T.O.; Pandhal, J.; Vaidyanathan, S. Microwave-Assisted Extraction for Microalgae: From Biofuels to Biorefinery. Biology 2018, 7, 18. [Google Scholar] [CrossRef][Green Version]
  202. Siahaan, E.A.; Chun, B.S. Innovative Alternative Technology for Fucoxanthin Recovery. In Encyclopedia of Marine Biotechnology; John Wiley & Sons, Inc.: New York, NY, USA, 2020; pp. 3213–3227. [Google Scholar] [CrossRef]
  203. Guler, B.A.; Deniz, I.; Demirel, Z.; Yesil-Celiktas, O.; Imamoglu, E. A novel subcritical fucoxanthin extraction with a biorefinery approach. Biochem. Eng. J. 2019, 153, 107403. [Google Scholar] [CrossRef]
  204. Sun, J.; Zhou, C.; Cheng, P.; Zhu, J.; Hou, Y.; Li, Y.; Zhang, J.; Yan, X. A simple and efficient strategy for fucoxanthin extraction from the microalga Phaeodactylum tricornutum. Algal Res. 2021, 61, 102610. [Google Scholar] [CrossRef]
  205. Pasquet, V.; Chérouvrier, J.-R.; Farhat, F.; Thiéry, V.; Piot, J.M.; Bérard, J.-B.; Kaas, R.; Serive, B.; Patrice, T.; Cadoret, J.-P.; et al. Study on the microalgal pigments extraction process: Performance of microwave assisted extraction. Process Biochem. 2011, 46, 59–67. [Google Scholar] [CrossRef][Green Version]
  206. Xiao, X.; Si, X.; Yuan, Z.; Xu, X.; Li, G. Isolation of fucoxanthin from edible brown algae by microwave-assisted extraction coupled with high-speed countercurrent chromatography. J. Sep. Sci. 2012, 35, 2313–2317. [Google Scholar] [CrossRef]
  207. Plaza, M.; Santoyo, S.; Jaime, L.; Reina, G.G.-B.; Herrero, M.; Señoráns, F.J.; Ibáñez, E. Screening for bioactive compounds from algae. J. Pharm. Biomed. Anal. 2010, 51, 450–455. [Google Scholar] [CrossRef]
  208. Shang, Y.F.; Kim, S.M.; Lee, W.J.; Um, B.-H. Pressurized liquid method for fucoxanthin extraction from Eisenia bicyclis (Kjellman) Setchell. J. Biosci. Bioeng. 2011, 111, 237–241. [Google Scholar] [CrossRef]
  209. Taucher, J.; Baer, S.; Schwerna, P.; Hofmann, D.; Hümmer, M.; Becker, R.B.A.A. Cell Disruption and Pressurized Liquid Extraction of Carotenoids from Microalgae. J. Thermodyn. Catal. 2016, 7, 158–165. [Google Scholar] [CrossRef][Green Version]
  210. Olaizola, M. Commercial production of astaxanthin from Haematococcus pluvialis using 25,000-liter outdoor photobioreactors. J. Appl. Phycol. 2000, 12, 499–506. [Google Scholar] [CrossRef]
  211. Billakanti, J.; Catchpole, O.; Fenton, T.A.; Mitchell, K.A.; MacKenzie, A.D. Enzyme-assisted extraction of fucoxanthin and lipids containing polyunsaturated fatty acids from Undaria pinnatifida using dimethyl ether and ethanol. Process Biochem. 2013, 48, 1999–2008. [Google Scholar] [CrossRef]
  212. Ruiz-Domínguez, M.C.; Salinas, F.; Medina, E.; Rincón, B.; Martín, M.; Gutiérrez, M.C.; Cerezal-Mezquita, P. Supercritical Fluid Extraction of Fucoxanthin from the Diatom Phaeodactylum tricornutum and Biogas Production through Anaerobic Digestion. Mar. Drugs 2022, 20, 127. [Google Scholar] [CrossRef] [PubMed]
  213. Knorr, S.T.A.D. Pulsed electric fields as a pretreatment technique in drying processes. Stewart Postharvest Rev. 2006, 2, 1–6. [Google Scholar] [CrossRef]
  214. Parniakov, O.; Barba, F.J.; Grimi, N.; Marchal, L.; Jubeau, S.; Lebovka, N.; Vorobiev, E. Pulsed electric field and pH assisted selective extraction of intracellular components from microalgae Nannochloropsis. Algal Res. 2015, 8, 128–134. [Google Scholar] [CrossRef]
  215. Jaeschke, D.P.; Menegol, T.; Rech, R.; Mercali, G.D.; Marczak, L.D.F. Carotenoid and lipid extraction from Heterochlorella luteoviridis using moderate electric field and ethanol. Process Biochem. 2016, 51, 1636–1643. [Google Scholar] [CrossRef]
  216. Grimi, N.; Dubois, A.; Marchal, L.; Jubeau, S.; Lebovka, N.; Vorobiev, E. Selective extraction from microalgae Nannochloropsis sp. using different methods of cell disruption. Bioresour. Technol. 2014, 153, 254–259. [Google Scholar] [CrossRef]
  217. Khoo, K.S.; Ooi, C.W.; Chew, K.W.; Chia, S.R.; Foo, S.C.; Ng, H.S.; Show, P.L. Extraction of fucoxanthin from Chaetoceros calcitrans by electropermeabilization-assisted liquid biphasic flotation system. J. Chromatogr. A 2022, 1668, 462915. [Google Scholar] [CrossRef]
  218. Pierobon, S.C.; Cheng, X.; Graham, P.J.; Nguyen, B.; Karakolis, E.G.; Sinton, D. Emerging microalgae technology: A review. Sustain. Energy Fuels 2017, 2, 13–38. [Google Scholar] [CrossRef]
  219. Teramukai, K.; Kakui, S.; Beppu, F.; Hosokawa, M.; Miyashita, K. Effective extraction of carotenoids from brown seaweeds and vegetable leaves with edible oils. Innov. Food Sci. Emerg. Technol. 2020, 60, 102302. [Google Scholar] [CrossRef]
  220. Maeda, H.; Hosokawa, M.; Sashima, T.; Miyashita, K. Dietary Combination of Fucoxanthin and Fish Oil Attenuates the Weight Gain of White Adipose Tissue and Decreases Blood Glucose in Obese/Diabetic KK-Ay Mice. J. Agric. Food Chem. 2007, 55, 7701–7706. [Google Scholar] [CrossRef]
  221. Choi, S.-A.; Oh, Y.-K.; Lee, J.; Sim, S.J.; Hong, M.E.; Park, J.-Y.; Kim, M.-S.; Kim, S.W.; Lee, J.-S. High-efficiency cell disruption and astaxanthin recovery from Haematococcus pluvialis cyst cells using room-temperature imidazolium-based ionic liquid/water mixtures. Bioresour. Technol. 2018, 274, 120–126. [Google Scholar] [CrossRef] [PubMed]
  222. Bi, W.; Tian, M.; Zhou, J.; Row, K.H. Task-specific ionic liquid-assisted extraction and separation of astaxanthin from shrimp waste. J. Chromatogr. B 2010, 878, 2243–2248. [Google Scholar] [CrossRef] [PubMed]
  223. Costa Gomes, M. Deep Eutectic Solvents for Medicine, Gas Solubilization and Extraction of Natural Substances; Springer International Publishing: New York, NY, USA, 2021. [Google Scholar]
  224. Fu, X.; Wang, D.; Belwal, T.; Xu, Y.; Li, L.; Luo, Z. Sonication-synergistic natural deep eutectic solvent as a green and efficient approach for extraction of phenolic compounds from peels of Carya cathayensis Sarg. Food Chem. 2021, 355, 129577. [Google Scholar] [CrossRef] [PubMed]
  225. Rodrigues, L.A.; Pereira, C.V.; Leonardo, I.C.; Fernández, N.; Gaspar, F.B.; Silva, J.M.; Reis, R.L.; Duarte, A.R.C.; Paiva, A.; Matias, A.A. Terpene-Based Natural Deep Eutectic Systems as Efficient Solvents to Recover Astaxanthin from Brown Crab Shell Residues. ACS Sustain. Chem. Eng. 2020, 8, 2246–2259. [Google Scholar] [CrossRef]
  226. Obluchinskaya, E.; Pozharitskaya, O.; Zakharova, L.; Daurtseva, A.; Flisyuk, E.; Shikov, A. Efficacy of Natural Deep Eutectic Solvents for Extraction of Hydrophilic and Lipophilic Compounds from Fucus vesiculosus. Molecules 2021, 26, 4198. [Google Scholar] [CrossRef]
  227. Gallego, R.; Tardif, C.; Parreira, C.; Guerra, T.; Alves, M.J.; Ibáñez, E.; Herrero, M. Simultaneous extraction and purification of fucoxanthin from Tisochrysis lutea microalgae using compressed fluids. J. Sep. Sci. 2020, 43, 1967–1977. [Google Scholar] [CrossRef]
  228. Chen, C.-R.; Lin, D.-M.; Chang, C.-M.J.; Chou, H.-N.; Wu, J.-J. Supercritical carbon dioxide anti-solvent crystallization of fucoxanthin chromatographically purified from Hincksia mitchellae P.C. Silva. J. Supercrit. Fluids 2017, 119, 1–8. [Google Scholar] [CrossRef]
  229. Gómez-Loredo, A.; Gonzalez-Valdez, J.; Rito-Palomares, M. Insights on the downstream purification of fucoxanthin, a microalgal carotenoid, from an aqueous two-phase system stream exploiting ultrafiltration. J. Appl. Phycol. 2014, 27, 1517–1523. [Google Scholar] [CrossRef]
  230. Iqbal, M.; Tao, Y.; Xie, S.; Zhu, Y.; Chen, D.; Wang, X.; Huang, L.; Peng, D.; Sattar, A.; Shabbir, M.A.B.; et al. Aqueous two-phase system (ATPS): An overview and advances in its applications. Biol. Proced. Online 2016, 18, 1–18. [Google Scholar] [CrossRef][Green Version]
  231. Espitia-Saloma, E.; Villegas, P.V.; Aguilar, O.; Rito-Palomares, M. Continuous aqueous two-phase systems devices for the recovery of biological products. Food Bioprod. Process. 2014, 92, 101–112. [Google Scholar] [CrossRef]
  232. Hatti-Kaul, R. Aqueous Two-Phase Systems: Methods and Protocols; Springer Science & Business Media: New York, NY, USA, 2000; ISBN 978-1-59259-028-5. [Google Scholar]
  233. Albertsson, P.A. Partition of cell particles and macromolecules in polymer two-phase systems. Adv. Protein Chem. 1970, 24, 309–341. [Google Scholar] [PubMed]
  234. Chen, J.-P.; Lee, M.-S. Enhanced production of Serratia marcescens chitinase in PEG/dextran aqueous two-phase systems. Enzym. Microb. Technol. 1995, 17, 1021–1027. [Google Scholar] [CrossRef]
  235. Helfrich, M.R.; El-Kouedi, M.; Etherton, M.R.; Keating, C.D. Partitioning and Assembly of Metal Particles and Their Bioconjugates in Aqueous Two-Phase Systems. Langmuir 2005, 21, 8478–8486. [Google Scholar] [CrossRef] [PubMed]
  236. Benavides, J.; Rito-Palomares, M. Simplified two-stage method to B-phycoerythrin recovery from Porphyridium cruentum. J. Chromatogr. B 2006, 844, 39–44. [Google Scholar] [CrossRef] [PubMed]
  237. Schmidt, A.; Ventom, A.; Asenjo, J. Partitioning and purification of α-amylase in aqueous two-phase systems. Enzym. Microb. Technol. 1994, 16, 131–142. [Google Scholar] [CrossRef]
  238. Gómez-Loredo, A.; González-Valdez, J.; González-González, M.; Benavides, J.; Rito-Palomares, M. Practical experiences from the bench-scale implementation of a bioprocess for fucoxanthin production. J. Chem. Technol. Biotechnol. 2017, 93, 2033–2039. [Google Scholar] [CrossRef]
  239. Gómez-Loredo, A.; Benavides, J.; Rito-Palomares, M. Partition behavior of fucoxanthin in ethanol-potassium phosphate two-phase systems. J. Chem. Technol. Biotechnol. 2014, 89, 1637–1645. [Google Scholar] [CrossRef]
  240. Kim, S.M.; Shang, Y.F.; Um, B.-H. A preparative method for isolation of fucoxanthin from Eisenia bicyclis by centrifugal partition chromatography. Phytochem. Anal. 2011, 22, 322–329. [Google Scholar] [CrossRef]
  241. Beppu, F.; Niwano, Y.; Tsukui, T.; Hosokawa, M.; Miyashita, K. Single and repeated oral dose toxicity study of fucoxanthin (FX), a marine carotenoid, in mice. J. Toxicol. Sci. 2009, 34, 501–510. [Google Scholar] [CrossRef][Green Version]
  242. Iio, K.; Okada, Y.; Ishikura, M. Single and 13-Week Oral Toxicity Study of Fucoxanthin Oil from Microalgae in Rats. Food Hyg. Saf. Sci. 2011, 52, 183–189. [Google Scholar] [CrossRef]
  243. Yusof, Z.; Khong, N.M.H.; Choo, W.S.; Foo, S.C. Opportunities for the marine carotenoid value chain from the perspective of fucoxanthin degradation. Food Chem. 2022, 383, 132394. [Google Scholar] [CrossRef] [PubMed]
  244. Wang, C.; Chen, X.; Nakamura, Y.; Yu, C.; Qi, H. Fucoxanthin activities motivate its nano/micro-encapsulation for food or nutraceutical application: A review. Food Funct. 2020, 11, 9338–9358. [Google Scholar] [CrossRef] [PubMed]
  245. Cordenonsi, L.M.; Santer, A.; Sponchiado, R.M.; Wingert, N.R.; Raffin, R.P.; Schapoval, E.E.S. Amazonia Products in Novel Lipid Nanoparticles for Fucoxanthin Encapsulation. AAPS PharmSciTech 2019, 21, 32. [Google Scholar] [CrossRef]
  246. Foo, S.C.; Khong, N.M.; Yusoff, F.M. Physicochemical, microstructure and antioxidant properties of microalgae-derived fucoxanthin rich microcapsules. Algal Res. 2020, 51, 102061. [Google Scholar] [CrossRef]
  247. Koo, S.Y.; Mok, I.-K.; Pan, C.-H.; Kim, S.M. Preparation of Fucoxanthin-Loaded Nanoparticles Composed of Casein and Chitosan with Improved Fucoxanthin Bioavailability. J. Agric. Food Chem. 2016, 64, 9428–9435. [Google Scholar] [CrossRef] [PubMed]
  248. Li, D.; Liu, Y.; Ma, Y.; Liu, Y.; Wang, S.; Guo, Z.; Li, J.; Wang, Y.; Tan, B.; Wei, Y. Fabricating hydrophilic fatty acid-protein particles to encapsulate fucoxanthin: Fatty acid screening, structural characterization, and thermal stability analysis. Food Chem. 2022, 382, 132311. [Google Scholar] [CrossRef] [PubMed]
  249. Ma, Z.; Zhao, Y.; Khalid, N.; Shu, G.; Neves, M.A.; Kobayashi, I.; Nakajima, M. Comparative study of oil-in-water emulsions encapsulating fucoxanthin formulated by microchannel emulsification and high-pressure homogenization. Food Hydrocoll. 2020, 108, 105977. [Google Scholar] [CrossRef]
  250. Oliyaei, N.; Moosavi-Nasab, M.; Tamaddon, A.M.; Fazaeli, M. Double encapsulation of fucoxanthin using porous starch through sequential coating modification with maltodextrin and gum Arabic. Food Sci. Nutr. 2020, 8, 1226–1236. [Google Scholar] [CrossRef]
  251. Rehman, A.Q.T.; Jafari, S.M.; Assadpour, E.Q.S.; Aadil, R.M.; Iqbal, M.W.; Rashed, M.M.A.; Sajid, B.; Mushtaq, W.A. Carotenoid-loaded nanocarriers: A comprehensive review. Adv. Colloid Interface Sci. 2020, 275, 102048. [Google Scholar] [CrossRef]
  252. Roychoudhury, P.; Dąbek, P.; Gloc, M.; Golubeva, A.; Dobrucka, R.; Kurzydłowski, K.; Witkowski, A. Reducing Efficiency of Fucoxanthin in Diatom Mediated Biofabrication of Gold Nanoparticles. Materials 2021, 14, 4094. [Google Scholar] [CrossRef]
  253. Wang, C.; Ren, J.; Song, H.; Chen, X.; Qi, H. Characterization of whey protein-based nanocomplex to load fucoxanthin and the mechanism of action on glial cells PC12. LWT 2021, 151, 112208. [Google Scholar] [CrossRef]
  254. Bayu, A.; Rachman, A.; Noerdjito, D.R.; Putra, M.Y.; Widayatno, W.B. High-value chemicals from marine diatoms: A biorefinery approach. IOP Conf. Series Earth Environ. Sci. 2020, 460, 012012. [Google Scholar] [CrossRef]
  255. Centre d’Etude et de Valorisation des Algues. Macroalgues et Microalgues Alimentaires—Statut Règlementaire En France et En Europe: Synthèse CEVA; CEVA: Pleubian, France, 2019. [Google Scholar]
  256. Faisal Hossain, M.; Mamoon, R.; Thomas, B.; Mohammed, A.; Winnie, W.; Adeshina, K.K.; Rajjit, S.; Michael, J.; Shamly, A. Evaluation of Fucoxanthin Content in Popular Weight Loss Supplements: The Case for Stricter Regulation of Dietary Supplements. J. Obes. Weight. Medicat. 2019, 5, 1–6. [Google Scholar] [CrossRef]
  257. Miyashita, K.; Beppu, F.; Hosokawa, M.; Liu, X.; Wang, S. Nutraceutical characteristics of the brown seaweed carotenoid fucoxanthin. Arch. Biochem. Biophys. 2020, 686, 108364. [Google Scholar] [CrossRef] [PubMed]
  258. Lourenço-Lopes, C.; Fraga-Corral, M.; Jimenez-Lopez, C.; Pereira, A.; Garcia-Oliveira, P.; Carpena, M.; Prieto, M.; Simal-Gandara, J. Metabolites from Macroalgae and Its Applications in the Cosmetic Industry: A Circular Economy Approach. Resources 2020, 9, 101. [Google Scholar] [CrossRef]
  259. Lee, Y.-J.; Nam, G.-W. Sunscreen Boosting Effect by Solid Lipid Nanoparticles-Loaded Fucoxanthin Formulation. Cosmetics 2020, 7, 14. [Google Scholar] [CrossRef][Green Version]
  260. Lee, K.-T.; Lee, Y.; Jeong, J.-H.; Jo, B.-K. New Anti-Wrinkle Cosmetics. J. Soc. Cosmet. Sci. Korea 2002, 28, 71–79. [Google Scholar]
  261. Maeda, H.; Hosokawa, M.; Sashima, T.; Funayama, K.; Miyashita, K. Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues. Biochem. Biophys. Res. Commun. 2005, 332, 392–397. [Google Scholar] [CrossRef]
  262. Maeda, H.; Tsukui, T.; Sashima, T.; Hosokawa, M.; Miyashita, K. Seaweed carotenoid, fucoxanthin, as a multi-functional nutrient. Asia Pac. J. Clin. Nutr. 2008, 17, 196–199. [Google Scholar]
  263. Himms-Hagen, J. Brown adipose tissue thermogenesis: Interdisciplinary studies. FASEB J. 1990, 4, 2890–2898. [Google Scholar] [CrossRef]
  264. Martinez-Teipel, B.; Bouhrir, S. Reshaping Body Care with Biotech Microalgae. Personal Care 2021, 22, 59–63. [Google Scholar]
  265. Market Reports World Global Fucoxanthin Market. 2017. Available online: https://www.marketreportsworld.com/global-fucoxanthin-market-10565168 (accessed on 18 September 2019).
Figure 1. Chemical structure of the fucoxanthin molecule.
Figure 1. Chemical structure of the fucoxanthin molecule.
Marinedrugs 20 00222 g001
Figure 2. Isomers of fucoxanthin, all-trans fucoxanthin, 9′-cis fucoxanthin, 13-cis fucoxanthin, 13′-cis fucoxanthin.
Figure 2. Isomers of fucoxanthin, all-trans fucoxanthin, 9′-cis fucoxanthin, 13-cis fucoxanthin, 13′-cis fucoxanthin.
Marinedrugs 20 00222 g002
Figure 3. Hypothetic pathway of the fucoxanthin final synthesis reactions. Orange: genes implied in biosynthesis.
Figure 3. Hypothetic pathway of the fucoxanthin final synthesis reactions. Orange: genes implied in biosynthesis.
Marinedrugs 20 00222 g003
Figure 4. Schematic illustration of a close tubular air-lift photobioreactor and main culture parameters.
Figure 4. Schematic illustration of a close tubular air-lift photobioreactor and main culture parameters.
Marinedrugs 20 00222 g004
Figure 5. Example of a centrifugal partition chromatography purification process for the pigment separation of an extract of T. lutea.
Figure 5. Example of a centrifugal partition chromatography purification process for the pigment separation of an extract of T. lutea.
Marinedrugs 20 00222 g005
Figure 6. Applications and current market of fucoxanthin in food, cosmetics and medicine.
Figure 6. Applications and current market of fucoxanthin in food, cosmetics and medicine.
Marinedrugs 20 00222 g006
Table 1. Biological activities of fucoxanthin—studies of 2020–2021. The notation “p“ means the fucoxanthin was purchased and not directly purified from algae within the study.
Table 1. Biological activities of fucoxanthin—studies of 2020–2021. The notation “p“ means the fucoxanthin was purchased and not directly purified from algae within the study.
PropertySource of FucoxanthinTargetReference
Anti-cancerpMice pancreatic cancer cells[45]
pHamster pancreatic cancer cells[46]
pMice colorectal cancer cells[52,53]
pHuman colon cancer cells[54,55]
pOral squamous cancer cells (KB)[56]
pHuman glioblastoma cells (U87MG)[57]
Laminaria japonicaHuman lung cancer cells[58]
pHuman lung and cervical cancer cells[59]
pNasopharyngeal carcinoma cells[60]
Anti-inflammatorypInflammation of mice tracheal epithelial cells[61]
pInflammation in non-alcoholic fatty liver disease[62,63]
Sargassum fusiformisParticulate matter-induced inflammation[64]
Tisochrysis lutea, brown seaweedsLipopolysaccharide (LPS)-
stimulated RAW264.7 macrophages
[47,65,66]
pNeuroinflammatory response in induced-Parkinson’s disease[67]
pAcute lung injury inflammation[68]
Cylindrotheca closteriumImmunocytes, enterocytes, mesenchymal stem cells[69]
Phaeodactylum tricornutumPro-inflammatory cytokines[70]
pPAMP lipopolysaccharide-induced uveitis inflammation[71]
Anti-obesitypInsulin resistance of obese mice[72]
Sargassum siliquosumDiet-induced obesity in rats[73]
pGut microbiota in high-fat diet-fed mice[74]
Plocamium telfairiaeHigh-fat diet-fed mice[75]
Anti-diabetesSargassum angustifoliumStreptozotocin-nicotinamide-induced type 2 diabetic mice[76]
Protective effectspdexamethasone-induced myotubes atrophy[77]
pNeurodegenerative disorders[78]
p6-OHDA-Induced Neurotoxicity[79]
Sargassum honeriMethamphetamine-induced neurotoxicity[80]
pHigh glucose-induced oxidative stress[81]
pIrradiated mice[82]
pCalcification of heart valve interstitial cells[83]
pMacular degeneration and retinal pigment epithelial cell senescence[84]
pAtopic dermatitis symptoms[85]
pFibroblasts cellular senescence[86]
pIschemia-reperfusion injury in kidney[87]
pUV-B irradiation induced retinal Müller cells[88]
Anti-oxidant 20-year meta-analysis review[89]
Anti-microbialThalassiosira sp., Chaetoceroes sp.Pathogenic bacteria (Staphylococcus aureus, Escherichia coli)[90]
p20 bacterial species (Streptococcus agalactiae, Staphylococcus epidermidis…)[91]
preview[92]
Anti-AlzheimerSargassum horneriAβ oligomers-induced neurotoxicity[93]
Anti-osteoclastogenesispMAP kinase, Nrf2 signaling[94]
Anti-urolithiaticpEthylene glycol-induced renal calculus in rats[95]
Anti-fibrogenicpHepatic stellate cells[96]
Table 2. Microalgae species producing fucoxanthin in dried and fresh sample condition—studies of 2020–2022. The notation “-“ means that the data was not available.
Table 2. Microalgae species producing fucoxanthin in dried and fresh sample condition—studies of 2020–2022. The notation “-“ means that the data was not available.
Species Fx Content
(mg·g−1 Dry Weight)
Fx Productivity (mg·L−1·Day−1)ConditionReference
Tisochrysis luteahaptophyte16.0513.75dried[112]
Tisochrysis luteahaptophyte6.661.82dried[113]
Tisochrysis luteahaptophyte10.019.81dried[114]
Tisochrysis luteahaptophyte13.09-dried[115]
Tisochrysis luteahaptophyte16.302.77dried[116]
Tisochrysis luteahaptophyte17.801.14dried[117]
Tisochrysis luteahaptophyte79.40-dried[111]
Tisochrysis luteahaptophyte5.40-dried[118]
Pavlova lutherihaptophyte20.864.88dried[119]
Isochrysis zhangjiangensishaptophyte22.63.06dried[120]
Phaeodactylum tricornutumdiatom13.301.41dried[117]
Phaeodactylum tricornutumdiatom7.00-dried[118]
Phaeodactylum tricornutumdiatom13.008.22dried[121]
Phaeodactylum tricornutumdiatom16.30-dried[122]
Phaeodactylum tricornutumdiatom17.55-dried[123]
Phaeodactylum tricornutumdiatom16.13-dried[124]
Phaeodactylum tricornutumdiatom21.90-fresh[125]
Phaeodactylum tricornutumdiatom21.20-dried[126]
Chaetoceros calcitransdiatom17.51-dried[127]
Stauroneis sp.diatom11.80-dried[128]
Stauroneis sp.diatom5.90-dried[129]
Thalassiosira weissflogiidiatom9.005.10dried[130]
Odontella auritadiatom16.209.41dried[131]
Amphora capitellatadiatom41.83-dried[132]
Nitzschia laevisdiatom12.20-dried[133]
Conticribra weissflogiidiatom10.00-fresh[134]
Sellaphora minimadiatom7.601.2fresh[135]
Nitzschia paeladiatom5.700.60fresh[135]
Chaetoceros gracilisdiatom15.43.82fresh[136]
Table 3. Carotenoids extraction with ionic liquids.
Table 3. Carotenoids extraction with ionic liquids.
SaltCarotenoids ExtractedReference
DACARB (diallyammonium diallycarbamate)Fucoxanthin[127]
BF4 (tetrafluoborate)Astaxanthin[222]
MS (methylsulfate)Astaxanthin[222]
ethanol + 1-n-butyl-3-methylimidazolium + BrAstaxanthin[221]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Pajot, A.; Hao Huynh, G.; Picot, L.; Marchal, L.; Nicolau, E. Fucoxanthin from Algae to Human, an Extraordinary Bioresource: Insights and Advances in up and Downstream Processes. Mar. Drugs 2022, 20, 222. https://doi.org/10.3390/md20040222

AMA Style

Pajot A, Hao Huynh G, Picot L, Marchal L, Nicolau E. Fucoxanthin from Algae to Human, an Extraordinary Bioresource: Insights and Advances in up and Downstream Processes. Marine Drugs. 2022; 20(4):222. https://doi.org/10.3390/md20040222

Chicago/Turabian Style

Pajot, Anne, Gia Hao Huynh, Laurent Picot, Luc Marchal, and Elodie Nicolau. 2022. "Fucoxanthin from Algae to Human, an Extraordinary Bioresource: Insights and Advances in up and Downstream Processes" Marine Drugs 20, no. 4: 222. https://doi.org/10.3390/md20040222

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop