Bioactive Metabolites from Portuguese Atlantic Seaweeds: Diversity, Chemical Profiles, and Emerging Biotechnological Applications

Abstract

The Portuguese Atlantic coast harbors a remarkably diverse macroalgal flora, shaped by the intersection of Lusitanian, Mediterranean, and boreal biogeographic influences. This diversity is reflected in the rich repertoire of secondary metabolites produced by local seaweeds, including halogenated compounds, terpenoids, phlorotannins, mycosporine like amino acids, sulfated polysaccharides, and unique phenolic structures. These metabolites exhibit a wide range of bioactivities, antioxidant, anti-inflammatory, antimicrobial, antiviral, antifouling, antitumoral, and neuroprotective, positioning Portuguese seaweeds as promising sources of novel bioactive agents. This review synthesizes the current state of knowledge on the chemical diversity and biological properties of metabolites isolated from seaweeds along the Portuguese Atlantic coast. We examine species-specific metabolite profiles, ecological drivers of chemical variability, and advances in extraction, purification, and structural elucidation. Emerging applications in pharmaceuticals, nutraceuticals, cosmeceuticals, and sustainable biomaterials are discussed, alongside the potential of seaweed derived compounds to support blue bioeconomy development. Finally, we identify research gaps and propose future directions for bioprospecting, metabolomics, and biotechnological exploitation of this underexplored marine resource.

1. Introduction

The Portuguese Atlantic coast hosts one of the richest and most ecologically diverse macroalgal floras in Europe, shaped by the confluence of temperate and subtropical biogeographic influences. This unique setting supports a high diversity of Rhodophyta, Phaeophyceae, and Chlorophyta, many of which are known producers of structurally diverse and biologically active metabolites. A review focused on Portuguese Atlantic seaweeds is timely and highly relevant, as this region remains underrepresented in global metabolite research despite its exceptional biodiversity and long history of phycological study. This revision will synthesize current knowledge on the chemical diversity, ecological functions, and biotechnological potential of metabolites from Portuguese seaweeds, highlighting their relevance for pharmaceuticals, nutraceuticals, cosmeceuticals, and blue bioeconomy innovation [1,2,3].

Marine macroalgae are recognized as prolific producers of structurally diverse and biologically active metabolites, including polysaccharides, phenolics, lipids, terpenoids, and halogenated compounds. These metabolites exhibit a wide range of bioactivities, antioxidant, antimicrobial, antiviral, anti-inflammatory, and antitumoral, making seaweeds valuable resources for natural product discovery and biotechnology [4]. Recent reviews highlight the pharmaceutical potential of seaweed-derived compounds, emphasizing their relevance as leads for drug development and as functional ingredients in nutraceutical and cosmeceutical formulations [5]. Studies conducted along the Portuguese coast have demonstrated strong antioxidant and antibacterial activities in extracts from multiple macroalgal species, reinforcing the importance of these organisms as reservoirs of bioactive agents with potential industrial applications. Furthermore, seaweed lipids from the Portuguese North Coast have been shown to possess health-promoting properties, including anti-inflammatory and cardioprotective effects, underscoring the multifunctional nature of macroalgal metabolites [6].

2. Biodiversity of Portuguese Atlantic Seaweeds

Biogeographic Context

The Portuguese Atlantic coast represents one of the most ecologically complex and biogeographically significant marine regions in Europe. Situated at the intersection of the cold-temperate North Atlantic, the warm-temperate Lusitanian province, and the subtropical Northeast Atlantic, Portugal forms a natural transition zone where species from contrasting climatic regimes coexist. This transitional character is a major driver of the exceptional macroalgal diversity observed along the Portuguese mainland and island territories [7,8].

The western coast of Portugal is strongly influenced by the Iberian Coastal Upwelling System, one of the most productive eastern boundary upwelling systems in the world. Seasonal upwelling events bring cold, nutrient-rich waters to the surface, supporting high primary productivity and favoring the persistence of cold-affinity macroalgal species typical of northern Europe, such as Ascophyllum, Laminaria, Saccharina, and Fucus spp. (Phaeophyceae) [9,10]. In contrast, the southern coast, particularly the Algarve, experiences warmer, more stratified waters influenced by the Mediterranean outflow and subtropical currents, enabling the establishment of warm-water taxa such as Sargassum, Rugulopteryx (Phaeophyceae), Asparagopsis (Rhodophyta), and Codium (Chlorophyta) species [11,12].

The interplay between upwelling intensity, sea surface temperature gradients, wave exposure, and coastal geomorphology creates a mosaic of ecological niches. Rocky shores, estuaries, sheltered coves, and exposed headlands each support distinct macroalgal assemblages. The western coast, characterized by high wave energy and strong upwelling, favors robust canopy-forming brown algae and extensive red algal turfs. Meanwhile, the southern coast, with its warmer waters and limestone substrates, supports a flora with greater subtropical affinity and higher representation of calcified red algae [2,7].

Portugal hosts a remarkably rich macroalgal flora, with over 700 recorded taxa across the three major phyla/class, Rhodophyta, Phaeophyceae, and Chlorophyta. Red algae (Rhodophyta) are particularly diverse, reflecting both the ecological heterogeneity of the coastline and the evolutionary history of the region. Brown algae (Phaeophyceae) include ecologically dominant canopy-forming species such as Fucus vesiculosus, Cystoseira (now Ericaria and Gongolaria) species, and Sargassum muticum, the latter representing a successful invasive species that has reshaped local communities. Green algae (Chlorophyta), including Ulva, Codium, and Bryopsis, are widespread and often respond rapidly to environmental change, making them useful indicators of ecological status [12].

The Portuguese archipelagos of Madeira and the Azores further enrich the national macroalgal diversity. These islands host a mixture of Atlantic, Macaronesian, and subtropical elements, including species absent from the mainland. Their volcanic substrates, clear waters, and unique oceanographic conditions support distinct assemblages and contribute significantly to the overall biodiversity of the Portuguese Exclusive Economic Zone (EEZ), one of the largest in Europe [12].

This biogeographic complexity translates directly into chemical diversity, as environmental gradients, evolutionary history, and ecological interactions shape the production of secondary metabolites. Many seaweeds, such as Asparagopsis armata (invasive species), Gelidium corneum (Rhodophyta), Rugulopteryx okamurae and Sargassum muticum (invasive species), Fucus spiralis (Phaeophyceae), and Codium tomentosum (Chlorophyta), are known to produce unique halogenated compounds, phlorotannins, sulfated polysaccharides, and terpenoids with significant bioactive potential. The coexistence of cold- and warm-affinity species within a relatively small geographic area makes Portugal an exceptional natural laboratory for studying macroalgal chemical ecology and a promising region for marine bioprospecting [2,12].

The Portuguese Atlantic coast hosts a diverse macroalgal flora, with several genera standing out due to their ecological relevance, abundance, and biotechnological potential. Among the brown algae (Phaeophyceae), the genera Fucus, Ericaria, Gongolaria (formerly Cystoseira), and Sargassum are particularly important. Fucus spiralis, F. vesiculosus, and F. limitaneus (formerly F. guiryi) dominate many intertidal rocky shores and are well-known sources of phlorotannins and fucoidans, compounds with antioxidant, anti-inflammatory, and antimicrobial properties [2]. Species of Ericaria and Gongolaria form structurally complex canopies in subtidal and lower-intertidal zones, contributing significantly to habitat formation and producing terpenoids and phenolic compounds of biotechnological interest [13]. S. muticum, although non-native, is now widespread along the Portuguese coast and has become a relevant biomass source for studies on bioactive polysaccharides and lipid fractions [14].

Within the red algae (Rhodophyta), several genera are noteworthy for both ecological dominance and industrial relevance. Gelidium corneum (Figure 1) is one of the most economically important species in Portugal due to its role as a primary source of agar, and it forms extensive subtidal beds along the northern and central coast [12]. Asparagopsis taxiformis and Asparagopsis armata, non-native species of the Portuguese coastline, are recognized for its production of halogenated compounds (Figure 2) with strong antimicrobial and antifouling activities [15]. Other key genera include Gracilaria, valued for agar and bioactive sulfated galactans, and Porphyra/Neopyropia, which are increasingly studied for their nutritional and antioxidant properties [16].

The green algae (Chlorophyta) are represented by genera such as Ulva, Codium, and Bryopsis. Ulva lactuca and related species are common in estuarine and coastal environments and are known for their ulvans (Figure 3), sulfated polysaccharides with immunomodulatory and antioxidant potential [14]. Codium tomentosum, a characteristic species of the Portuguese coast, is valued for its unique sulfated heteropolysaccharides, bioactive lipids, and potential applications in functional foods and cosmeceuticals [17]. Bryopsis plumosa and related species, though less abundant, are of interest due to their production of distinctive secondary metabolites [2,15]. Together, these genera represent the core of the Portuguese Atlantic macroalgal flora and constitute a rich reservoir of structurally diverse metabolites with promising applications in pharmaceuticals, nutraceuticals, cosmeceuticals, and other blue-bioeconomy sectors.

The chemical diversity of Portuguese Atlantic seaweeds is strongly shaped by the ecological conditions under which these species grow. Environmental factors such as light availability, temperature, nutrient regimes, hydrodynamics, and herbivory pressure influence the synthesis and accumulation of secondary metabolites. In upwelling-influenced coasts, such as western Portugal, cold and nutrient-rich waters enhance macroalgal productivity and can stimulate the production of phenolics, carotenoids, and sulfated polysaccharides, which function in photoprotection and oxidative stress mitigation [18].

Hydrodynamic exposure is another major driver of chemical variability. Seaweeds inhabiting wave-exposed rocky shores often produce higher levels of phenolic compounds and structural polysaccharides that increase tissue rigidity and resistance to mechanical stress. Conversely, species growing in sheltered or estuarine environments may invest more heavily in metabolites related to osmotic balance and defense against epiphytes and pathogens. For example, salinity and nutrient fluctuations influence the biochemical composition of Ulva and Codium, affecting the production of ulvans and sulfated heteropolysaccharides [19,20].

Biotic interactions also play a crucial role. Herbivory by gastropods, amphipods, and fish, can induce the synthesis of deterrent metabolites, including halogenated compounds in red algae such as Asparagopsis and norditerpene in brown algae such as Bifurcaria bifurcata (Figure 4) and Ericaria [21,22]. Competition for space and light on rocky substrates further shapes chemical strategies, with some species producing allelopathic compounds that inhibit the settlement or growth of competitors. Seasonal changes in community composition also contribute to temporal shifts in metabolite profiles, as species adjust their biochemical strategies to varying ecological pressures [23].

Together, these ecological drivers create a complex and dynamic chemical landscape, making the Portuguese Atlantic flora an exceptional natural system for studying the interplay between environment, physiology, and secondary metabolism. This ecological complexity directly enhances the biotechnological potential of Portuguese seaweeds, as environmental variability promotes the synthesis of structurally diverse and biologically active compounds [22].

3. Major Classes of Bioactive Metabolites

3.1. Rhodophyta

Red algae (Rhodophyta) are among the most chemically diverse marine macroalgae, producing a wide array of structurally unique metabolites with significant ecological and biotechnological relevance. Many species occurring along the Portuguese Atlantic coast, such as Asparagopsis armata, Gelidium corneum, Gracilaria gracilis (Figure 5), and Porphyra/Neopyropia spp., are well-known sources of halogenated compounds, mycosporine-like amino acids (MAAs), and sulfated galactans, each representing a major class of bioactive molecules with promising applications in pharmaceuticals, cosmeceuticals, and functional foods [24].

3.1.1. Halogenated Compounds

Halogenated metabolites are particularly abundant in several red algal genera, especially Asparagopsis, Plocamium, and Laurencia/Osmundea. These compounds include haloforms, halogenated ketones, halo-acids, and polyhalogenated monoterpenes, many of which exhibit strong antimicrobial, antifouling, and cytotoxic activities. In Asparagopsis, halogenated compounds function as potent chemical defenses against herbivores and pathogens, contributing to the ecological success of this species in both native and introduced ranges [21]. Their strong bioactivity has stimulated interest in applications such as natural antifouling agents and antimicrobial formulations.

Some examples are:

Dibromoacetic acid (DBAA)—abundant in Asparagopsis armata and A. taxiformis, with strong antimicrobial and antifouling activity;

Bromochloroacetic acid—another haloform produced by Asparagopsis spp.

Plocamium monoterpenes (e.g., plocamene A)—polyhalogenated monoterpenes from Plocamium cartilagineum;

Laurencia sesquiterpenes (e.g., elatol)—potent antifouling and cytotoxic halogenated sesquiterpenes from Laurencia/Osmundea.

3.1.2. Mycosporine-like Amino Acids (MAAs)

MAAs are small, water-soluble secondary metabolites that absorb ultraviolet radiation, functioning as natural sunscreens (see Figure 5). They are widely distributed among Rhodophyta, particularly in intertidal species exposed to high solar irradiance. MAAs such as shinorine, porphyra-334, and palythine provide photoprotection and antioxidant activity, making them attractive for use in cosmeceuticals, especially as eco-friendly UV-absorbing ingredients [25]. Species of Porphyra/Neopyropia, common along the Portuguese coast, are especially rich in MAAs and have been extensively studied for their photoprotective and anti-inflammatory potential.

3.1.3. Sulfated Galactans

Sulfated galactans, including agarans and carrageenans, are hallmark polysaccharides of red algae and represent one of the most commercially important classes of marine biopolymers. Gelidium corneum, abundant along the northern and central Portuguese coast, is a globally recognized source of high-quality agar, composed primarily of agarose and agaropectin [2,15]. Gracilaria species produce structurally distinct galactans with variable degrees of sulfation, which influence their antiviral, immunomodulatory, anticoagulant, and antioxidant activities [26]. The structural diversity of these polysaccharides, modulated by species identity, environmental conditions, and life-cycle stage, makes them highly versatile for applications in biotechnology, food engineering, and biomedical research.

3.2. Phaeophyceae

Brown algae (Phaeophyceae) constitute one of the most ecologically and chemically significant groups of macroalgae along the Portuguese Atlantic coast. They are particularly abundant in intertidal and subtidal rocky habitats, where genera such as Fucus, Ericaria, Gongolaria, Sargassum, and Bifurcaria play key structural and functional roles. These species are also recognized as prolific producers of bioactive metabolites, including phlorotannins, terpenoids, fucoidans, sulfated fucans, carotenoids, and lipophilic compounds, many of which exhibit strong antioxidant, anti-inflammatory, antimicrobial, antiviral, and antitumoral activities [22,27].

3.2.1. Phlorotannins

Phlorotannins are polyphenolic secondary metabolites unique to brown algae and are synthesized through the polymerization of phloroglucinol units via the acetate–malonate pathway. Although particularly abundant in Fucus spp. and Ascophyllum nodosum (Figure 6), these compounds are widely distributed across several other Phaeophyceae genera occurring along the Portuguese Atlantic coast, including Sargassum, Ericaria, Gongolaria, Cystoseira (sensu lato), Saccharina and Laminaria spp. Their ecological functions are diverse, acting as chemical defenses against herbivory, UV radiation, oxidative stress, and microbial colonization [28].

In addition to Fucus spiralis and F. vesiculosus, which are known to accumulate high levels of phlorotannins with potent antioxidant and anti-inflammatory properties, several other brown algae from Portuguese waters have demonstrated significant phlorotannin content. Species of Ericaria and Gongolaria (formerly Cystoseira), notably Ericaria selaginoides (formerly Cystoseira tamariscifolia) (Figure 7), Gongolaria baccata, and G. nodicaulis, produce complex phlorotannin fractions associated with strong antioxidant, antimicrobial, and photoprotective activities. These canopy-forming algae, common along rocky subtidal habitats, contribute substantially to the chemical diversity of coastal ecosystems [29].

Laminaria ochroleuca, a cold-affinity kelp thriving in upwelling-influenced northern and central Portugal, also contains phlorotannins that play a role in UV protection and tissue reinforcement. Meanwhile, S. muticum, an invasive species now widespread along the Portuguese coast, synthesizes phlorotannins that contribute to its competitive success and resistance to herbivory. Extracts from Sargassum spp. have shown notable antioxidant and anti-inflammatory effects, reinforcing their potential for biotechnological applications [30].

Collectively, phlorotannins from these diverse brown-algal taxa exhibit strong free-radical scavenging capacity, metal-chelating activity, and modulation of inflammatory pathways [31,32]. These properties support their growing relevance as functional ingredients in nutraceuticals, cosmeceuticals, and dermal protection products, particularly in formulations targeting oxidative stress, inflammation, and UV-induced skin damage.

3.2.2. Fucoidans and Sulfated Polysaccharides

Fucoidans are complex sulfated polysaccharides characteristic of brown algae and represent one of the most biologically versatile classes of marine biopolymers. They are primarily composed of L-fucose and sulfate groups, but may also contain galactose, mannose, xylose, uronic acids, and acetyl substituents, depending on species, tissue type, and environmental conditions [33]. These structural variations strongly influence their physicochemical properties and biological properties.

Along the Portuguese Atlantic coast, fucoidans have been extensively documented in several ecologically dominant brown-algal genera. Species of Fucus, including F. spiralis, F. vesiculosus, and F. limitaneus, produce highly sulfated fucans with potent antioxidant, anticoagulant, antiviral, and immunomodulatory activities. Their structural complexity, including branching patterns and sulfate distribution, contributes to their strong bioactivity and makes them promising candidates for pharmaceutical and nutraceutical applications [34]. Ascophyllum nodosum, although more abundant in northern European shores, also occurs in cooler Portuguese habitats and is recognized for producing fucoidans with well-characterized anti-inflammatory and antitumoral properties. S. muticum, an invasive species now widespread along the Portuguese coast, synthesizes fucoidans with distinctive fucose–galactose backbones and high sulfate content. Extracts from Portuguese Sargassum populations have demonstrated strong antioxidant and anticoagulant activities, reinforcing the species’ potential as a biomass source for bioactive polysaccharides [14].

Canopy-forming genera such as Ericaria and Gongolaria also produce structurally diverse sulfated polysaccharides, including fucoidans and heterofucans enriched in uronic acids. These compounds exhibit antimicrobial, antiviral, and anti-adhesive properties, contributing to the ecological success of these species in high-energy rocky environments [13]. L. ochroleuca (Figure 8), a kelp species common in northern and central Portugal, contains sulfated fucans and laminarans that play roles in stress tolerance and have shown immunomodulatory and antitumoral activities in bioassays. The biological activities of fucoidans and related sulfated polysaccharides are diverse and include anticoagulant, antithrombotic, antiviral, anti-inflammatory, antioxidant, and anticancer effects [33]. These activities are closely linked to structural features such as molecular weight, degree of sulfation, monosaccharide composition, and glycosidic linkages. Environmental factors, such as upwelling intensity, salinity, and seasonal variation, further modulate polysaccharide composition in Portuguese populations, creating a rich natural laboratory for exploring structure–function relationships.

Given their multifunctional bioactivity and biocompatibility, fucoidans and sulfated polysaccharides from brown algae hold significant promise for applications in pharmaceuticals, functional foods, cosmeceuticals, wound healing materials, and biodegradable biomaterials. Their abundance in local species, combined with Portugal’s extensive coastline and growing blue-bioeconomy initiatives, positions these compounds as strategic resources for sustainable biotechnological development.

3.2.3. Terpenoids

Terpenoids constitute one of the most structurally diverse and ecologically significant classes of secondary metabolites produced by brown algae. Derived from the mevalonate and methylerythritol phosphate (MEP) pathways, these compounds include mono-, sesqui-, di-, and meroterpenoids with a wide range of ecological functions and bioactivities. In marine environments, terpenoids act as chemical defenses against herbivores, fouling organisms, and microbial pathogens, and they also play roles in allelopathy and interspecific competition [21].

Along the Portuguese Atlantic coast, several Phaeophyceae genera are recognized for their rich terpenoid profiles. Bifurcaria bifurcata is one of the most chemically prolific species, producing a suite of linear diterpenes such as eleganolone, bifurcadiol, and bifurcatriol. These compounds exhibit potent cytotoxic, anti-inflammatory, and antimicrobial activities, and have been the subject of extensive chemical and pharmacological investigation [22]. The abundance of B. bifurcata along northern and central Portugal makes it a particularly valuable natural source of bioactive diterpenoids.

E. selaginoides, G. baccata, G. nodicaulis and Cystoseira humilis (Figure 9), are also well-known producers of meroditerpenoids such as cystoseirols, hydroquinones, and chromenes. These metabolites display strong antioxidant, antifouling, and cytotoxic properties, contributing to the ecological success of these canopy-forming algae in high-energy rocky habitats (Bertocci et al. 2010) [13]. Their chemical diversity has attracted interest for applications in antifoul coatings, anticancer research, and natural antioxidant formulations.

Dictyota dichotoma and related species are another important source of terpenoids, particularly diterpenes such as pachydictyol A (Figure 10), dictyol E, and dictyol B. These compounds have been shown to possess antiviral, antitumoral, and antifouling activities, and their ecological role in deterring herbivory is well documented [35,36,37]. Although Dictyota species are more abundant in warmer southern Portuguese waters, they contribute significantly to the chemical landscape of the region.

S. muticum produces sesquiterpenes and meroterpenoids that enhance their competitive ability and resistance to herbivores. Extracts from Sargassum species have demonstrated antioxidant, antimicrobial, and anti-inflammatory activities, reinforcing their potential as biomass sources for biotechnological applications [14].

3.2.4. Carotenoids and Lipophilic Compounds

Brown algae are major natural sources of carotenoids, with fucoxanthin being the most abundant and biologically relevant pigment. Fucoxanthin exhibits a broad spectrum of bioactivities, including antioxidant, anti-obesity, antidiabetic, anti-inflammatory, and anticancer effects, making it one of the most promising marine-derived carotenoids for health-related applications [38]. Along the Portuguese Atlantic coast, high fucoxanthin levels have been reported in S. muticum, F. vesiculosus, and G. baccata (Figure 11), species that are widely distributed across intertidal and subtidal habitats. In addition to carotenoids, these and other brown-algal taxa produce diverse lipophilic compounds, including polyunsaturated fatty acids, sterols, and terpenoid-derived lipids. Lipophilic extracts from Portuguese populations of S. muticum, F. vesiculosus, and Gongolaria spp. have demonstrated notable biological activities, particularly anti-inflammatory, antioxidant, and cardioprotective effects, underscoring their potential as functional ingredients in nutraceutical and cosmeceutical formulations [6].

3.2.5. Ecological and Biotechnological Relevance

The chemical diversity of Portuguese Phaeophyceae is profoundly shaped by environmental gradients, including coastal upwelling intensity, hydrodynamic exposure, temperature fluctuations, and herbivory pressure. These ecological forces modulate metabolic pathways and stimulate the production of structurally diverse secondary metabolites with high biotechnological potential [23]. Consequently, brown algae inhabiting the Portuguese Atlantic coast represent an exceptional natural reservoir of bioactive compounds suitable for applications in pharmaceuticals, functional foods, cosmeceuticals, and sustainable biomaterials. Their ecological abundance, coupled with their remarkable chemical richness, underscores their strategic importance for the development and consolidation of Portugal’s emerging blue bioeconomy.

3.3. Chlorophyta

Green algae (Chlorophyta) represent an ecologically versatile and biochemically rich component of the Portuguese Atlantic macroalgal flora. Although less species-rich than Rhodophyta, they play essential roles in primary productivity, nutrient cycling, and habitat structuring across intertidal, subtidal, and estuarine systems. Their distribution along the Portuguese mainland and Island coasts is shaped by hydrodynamic exposure, salinity gradients, nutrient availability, and seasonal upwelling regimes, all of which influence growth dynamics and metabolite composition. Genera such as Ulva, Codium, Chaetomorpha, Cladophora, and Bryopsis are particularly prominent and have attracted increasing interest due to their biochemical diversity and biotechnological potential [39].

3.3.1. Primary and Secondary Metabolites

Chlorophyta synthesize a wide array of metabolites, including sulfated polysaccharides (ulvans and heteropolysaccharides), polyunsaturated fatty acids, sterols, pigments (chlorophylls and carotenoids), and distinctive peptides and terpenoids. These compounds underpin their ecological success, supporting rapid growth, tolerance to environmental stress, and resistance to epiphytism, and simultaneously enhance their value for industrial and biomedical applications [40].

3.3.2. Ulvans and Sulfated Polysaccharides

Species of Ulva are particularly well known for producing ulvans, complex sulfated polysaccharides composed mainly of rhamnose, glucuronic acid, iduronic acid, and xylose. Ulvan structure (see Figure 3) varies with species, season, and environmental conditions, influencing its physicochemical and biological properties. Recent reviews highlight the multifunctionality of ulvans, including antioxidant, immunomodulatory, antiviral, and anticoagulant activities [41,42]. Portuguese Ulva species such as U. rigida, U. compressa, and U. lactuca have been studied for their lipid and polysaccharide profiles, with polar lipid extracts demonstrating notable antioxidant and anti-inflammatory potential [43]. Advances in enzymatic characterization, including ulvan lyases, have further expanded opportunities for controlled depolymerization and generation of bioactive oligosaccharides [44].

3.3.3. Sulfated Heteropolysaccharides and Lipids in Codium

Codium tomentosum, a characteristic species of the Portuguese Atlantic, produces unique sulfated arabinogalactans with immunomodulatory, antiviral, and antitumoral activities. Recent studies have demonstrated the bioavailability and health-promoting properties of Codium extracts, including antioxidant and anti-inflammatory effects [45,46]. Additional work has explored nanoencapsulation strategies to enhance the stability and delivery of Codium bioactives for nutraceutical and cosmeceutical applications [47]. The species also contains bioactive lipids and sterols that contribute to its multifunctional biological profile.

3.3.4. Specialized Metabolites in Bryopsis and Other Genera

The discussion of primary and secondary metabolites in Chlorophyta provides a broad overview of the biochemical features shared across green macroalgae, highlighting the central roles of structural polysaccharides, lipids, pigments, and a variety of defensive or ecologically relevant secondary compounds. However, within this phylum, certain lineages exhibit metabolic profiles that diverge markedly from these general patterns and reveal a more specialized chemical ecology. This is particularly evident in siphonous green algae such as Bryopsis, Caulerpa, and Codium, whose coenocytic organization and ecological strategies give rise to a distinct suite of metabolites not typically encountered in other Chlorophyta. These genera produce structurally unusual terpenoids, acetogenins, and oxylipins that function in defense, allelopathy, and rapid wound responses, reflecting the unique physiological demands of their multinucleate, wall-less cellular architecture. Their chemical profiles are further shaped by interactions with associated microbiota, which may contribute to or modify the synthesis of certain compounds, underscoring the holobiont nature of their metabolic systems. By shifting the focus from general metabolic categories to the ecological and evolutionary particularities of siphonous green algae, this subsection highlights how specialized metabolites support competitive dominance, resistance to herbivory, and, in some cases, invasive potential. These distinctive chemical traits also enhance the biotechnological relevance of Bryopsis and related genera, positioning them as promising sources of novel bioactive molecules with applications in antifouling, antimicrobial, and therapeutic research [48,49].

3.3.5. Ecological and Biotechnological Relevance

The ecological versatility of Chlorophyta is closely linked to their biochemical plasticity. Environmental factors such as salinity fluctuations, nutrient pulses, hydrodynamic stress, and irradiance strongly influence metabolite synthesis, particularly the composition and sulfation patterns of ulvans and other cell-wall polysaccharides [42]. In upwelling-influenced regions of western Portugal, enhanced nutrient availability promotes rapid growth and elevated production of ulvans and antioxidant pigments, consistent with observations that nutrient regimes and light conditions modulate ulvan structure and bioactivity [41]. Estuarine species, exposed to variable salinity and eutrophication, often accumulate osmo-protective compounds and stress-responsive metabolites, reflecting the environmental sensitivity of ulvan biosynthesis and related metabolic pathways [44].

These ecological dynamics translate into significant biotechnological potential. Ulvans and sulfated arabinogalactans are increasingly recognized as multifunctional biopolymers suitable for pharmaceuticals, nutraceuticals, cosmeceuticals, and biodegradable materials due to their biocompatibility, antioxidant capacity, and structural versatility [42,45]. Their physicochemical properties support applications ranging from drug-delivery systems to dermal protection and tissue engineering. Lipid extracts from Ulva and Codium species have demonstrated anti-inflammatory and cardioprotective effects, reinforcing their value as functional ingredients [43,47]. Meanwhile, specialized metabolites from Bryopsis and other genera, such as terpenoids, peptides, and fatty-acid derivatives, offer promising leads for antimicrobial, antifouling, and anticancer research [23].

To provide a consolidated overview of the information presented in this section,

Table 1. Bioactive metabolites reported from Portuguese Atlantic seaweeds, with corresponding species, metabolite classes, extraction methods, and typical yields/concentration ranges (based on [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67]).

Species	Metabolite Class	Extraction Method (as Reported in Cited Studies)	Reported Yield/Concentration Range	Refs.
Fucus spiralis, F. vesiculosus, F. limitaneus	Phlorotannins, fucoidans, lipophilic compounds	Aqueous, ethanolic, methanolic extractions; hot-water extraction for polysaccharides	Phlorotannins abundant in phenolic-rich fractions; fucoidans typically high-sulfation polysaccharides	[2,13,22,27,34]
Ascophyllum nodosum	Phlorotannins, fucoidans	Aqueous and hydroalcoholic extraction	High phlorotannin content; fucoidans with strong bioactivity	[28,33,34]
Ericaria selaginoides, Gongolaria baccata, G. nodicaulis	Phlorotannins, meroditerpenoids, sulfated polysaccharides	Organic solvent extraction (ethanol, methanol), aqueous extraction	High phenolic content; structurally diverse meroditerpenoids	[13,29]
Sargassum muticum	Phlorotannins, fucoidans, lipophilic compounds	Methanolic, ethanolic, aqueous extractions	Fucoidans with high sulfate content; phenolic fractions with strong antioxidant activity	[14,22,30]
Laminaria ochroleuca	Laminarin, fucoidans, carotenoids (fucoxanthin)	Hot-water extraction, organic solvent extraction	Laminarin abundant in winter biomass; fucoxanthin present in lipophilic fractions	[33]
Bifurcaria bifurcata	Linear diterpenes (eleganolone, bifurcadiol, etc.)	Organic solvent extraction (hexane, dichloromethane, methanol)	High diterpene content in organic fractions	[21,22]
Dictyota dichotoma	Diterpenes (pachydictyol A, dictyols)	Organic solvent extraction	Diterpenes abundant in non-polar fractions	[37]
Asparagopsis armata	Halogenated compounds (haloforms, haloacids)	Aqueous and organic extraction	High concentrations of halogenated metabolites (e.g., dibromoacetic acid)	[15,21,24]
Gelidium corneum	Agar (agarose, agaropectin), phenolics	Hot-water extraction for agar; aqueous extraction for phenolics	High-quality agar; moderate antioxidant activity	[2,12,15,26]
Gracilaria gracilis	Sulfated galactans, MAAs	Aqueous extraction; organic extraction for pigments	Galactans with variable sulfation; MAAs present in UV-exposed tissues	[24,26]
Porphyra/Neopyropia spp.	MAAs (shinorine, porphyra-334), proteins	Aqueous extraction	High MAA content in intertidal populations	[25]
Ulva lactuca	Ulvans, carotenoids, lipids	Hot-water extraction for ulvans; organic extraction for lipids	Ulvans abundant; sulfation patterns vary with environment	[14,19,20]
Codium tomentosum	Sulfated heteropolysaccharides, lipids	Aqueous extraction; organic extraction for lipids	High lipid content; bioactive sulfated polysaccharides	[17,19,20]
Bryopsis plumosa	Specialized terpenoids, oxylipins	Organic solvent extraction	Presence of distinctive secondary metabolites	[2,15]

summarizes the main Portuguese Atlantic seaweed species, their major metabolite classes, extraction approaches, and reported concentration ranges.

4. Extraction, Isolation, and Structural Characterization

4.1. Green Extraction Technologies

The transition toward sustainable bioprocessing has accelerated the development of green extraction technologies for isolating bioactive metabolites from marine macroalgae. These approaches minimize solvent use, energy consumption, and environmental impact while improving extraction efficiency and preserving the structural integrity of thermolabile compounds. Such methods are particularly relevant for Portuguese Atlantic seaweeds, whose metabolites, polysaccharides, phenolics, pigments, lipids, and terpenoids, require gentle processing to maintain bioactivity.

Several green extraction technologies have already been applied to Portuguese Atlantic seaweeds, and including specific examples helps clarify their practical relevance. Ultrasound-assisted extraction has been used to enhance the recovery of phlorotannins and antioxidant compounds from Fucus vesiculosus and Fucus spiralis collected along the northern and central Portuguese coast, significantly improving yields while reducing solvent consumption. Pressurized liquid extraction has been applied to Sargassum muticum biomass harvested in western Portugal, enabling the efficient extraction of fucoidans and phenolic fractions under mild, environmentally friendly conditions. Supercritical CO₂ extraction has been explored for the isolation of lipophilic compounds, including fucoxanthin and polyunsaturated fatty acids, from Codium tomentosum and Ulva spp., demonstrating high selectivity and the advantage of solvent-free processing. Microwave-assisted extraction has also been tested on Gelidium corneum and Gracilaria gracilis to accelerate the release of sulfated galactans and antioxidant constituents using minimal energy input. Together, these examples illustrate how green extraction technologies are already contributing to the valorization of Portuguese seaweed resources and highlight their potential for future biorefinery applications [51,52].

4.1.1. Ultrasound-Assisted Extraction (UAE)

UAE enhances solvent penetration and mass transfer through acoustic cavitation, enabling rapid cell-wall disruption and efficient release of intracellular metabolites. Recent comparative studies demonstrate that UAE significantly improves yields of polysaccharides, phenolics, and pigments while reducing extraction time and solvent consumption [53]. UAE is especially effective for extracting ulvans, fucoidans, and phlorotannins, preserving their antioxidant and anti-inflammatory properties.

4.1.2. Microwave-Assisted Extraction (MAE)

MAE uses rapid dielectric heating to rupture algal tissues, offering high extraction efficiency with minimal thermal degradation. MAE has been shown to enhance the recovery of sulfated polysaccharides, carotenoids, and phenolic compounds, while maintaining their structural integrity [54]. Its reduced processing time and energy requirements make MAE a promising technology for large-scale seaweed biorefineries.

4.1.3. Pressurized Liquid Extraction (PLE)/Subcritical Water Extraction (SWE)

PLE and SWE employ elevated temperatures and pressures to increase solvent power while maintaining water in a liquid state. Subcritical water behaves as a tunable green solvent capable of extracting both polar and moderately non-polar compounds. Recent reviews highlight SWE as a highly selective and efficient method for recovering fucoidans, laminarans, phenolics, and pigments from seaweed [55]. Its low environmental footprint and scalability make it suitable for integrated biorefinery systems.

4.1.4. Supercritical Fluid Extraction (SFE)

SFE, typically using supercritical CO₂, provides a clean, solvent-free method for extracting lipophilic compounds, including carotenoids, sterols, and terpenoids. The addition of ethanol as a green co-solvent expands its applicability to moderately polar metabolites. Recent studies demonstrate that SFE yields high-purity fractions enriched in fucoxanthin, phytosterols, and bioactive lipids, with excellent preservation of thermolabile compounds [56].

4.1.5. Enzyme-Assisted Extraction (EAE)

EAE uses carbohydrases, proteases, or tailored enzyme cocktails to selectively degrade algal cell walls, improving the release of target metabolites. EAE has been shown to enhance the extraction of ulvans, sulfated arabinogalactans, proteins, and bioactive peptides, while operating under mild, food-grade conditions [57]. Its specificity and low environmental impact make EAE a key technology for sustainable seaweed bioprocessing.

4.1.6. Integrated Biorefinery Approaches

Recent techno-economic analyses emphasize the importance of multi-step green biorefineries, combining UAE, MAE, SWE, and EAE to sequentially recover polysaccharides, pigments, lipids, and phenolics from the same biomass. These integrated workflows maximize resource efficiency, reduce waste, and align with circular bioeconomy principles central to marine biotechnology development [51,57].

4.2. Chromatographic and Spectroscopic Methods

Chromatographic and spectroscopic techniques are essential tools for the isolation, purification, and structural elucidation of bioactive metabolites from marine macroalgae. Their combined application enables the separation of complex mixtures, identification of compound classes, and full structural characterization of both primary and secondary metabolites, including polysaccharides, phenolics, terpenoids, lipids, and halogenated compounds [59].

4.2.1. Chromatographic Techniques

High-Performance Liquid Chromatography (HPLC)

HPLC is the most widely used chromatographic method for profiling seaweed metabolites due to its high resolution, reproducibility, and compatibility with UV, fluorescence, and mass-spectrometric detectors. It is routinely applied for the quantification of phlorotannins, carotenoids, MAAs, and phenolic acids [60]. Reverse-phase HPLC (RP-HPLC) is particularly effective for separating moderately polar compounds such as phloroglucinol derivatives and meroterpenoids, while hydrophilic interaction chromatography (HILIC) enhances the separation of sulfated polysaccharides and MAAs [61].

Gas Chromatography–Mass Spectrometry (GC–MS)

GC–MS is widely used for volatile and semi-volatile metabolites, including halogenated compounds, fatty acids, sterols, and low-molecular-weight terpenoids. Derivatization techniques such as methylation or silylation improve the volatility of polar metabolites, enabling detailed profiling of lipid fractions and halogenated monoterpenes from genera such as Asparagopsis and Plocamium (Rhodophyta) [59].

Liquid Chromatography–Mass Spectrometry (LC–MS/MS)

LC–MS/MS provides high sensitivity and structural information for complex and thermolabile metabolites. It is increasingly used for targeted and untargeted seaweed metabolomics, enabling the identification of novel compounds and chemotaxonomic markers [61]. High-resolution MS (HRMS), including Orbitrap and Q-TOF systems, allows accurate mass determination and fragmentation analysis, essential for elucidating the structures of phlorotannins, sulfated polysaccharides, and meroditerpenoids.

Size-Exclusion Chromatography (SEC)

SEC is crucial for characterizing high-molecular-weight polysaccharides such as fucoidans, ulvans, and agarans. It provides information on molecular-weight distribution, polydispersity, and purity, parameters that strongly influence biological activity [60].

4.2.2. Spectroscopic Techniques

Nuclear Magnetic Resonance (NMR) Spectroscopy

NMR is the gold standard for structural elucidation of purified seaweed metabolites. ¹H and ¹³C NMR provide fundamental structural information. Two-dimensional NMR techniques (COSY, HSQC, HMBC, NOESY) enable detailed analysis of complex polysaccharides, terpenoids, and phenolic structures [59]. NMR is particularly valuable for determining sulfation patterns in fucoidans and ulvans, which correlate with bioactivity.

Fourier-Transform Infrared Spectroscopy (FTIR)

FTIR is widely used for rapid functional-group identification and quality assessment of polysaccharides, lipids, and phenolic extracts. It is especially useful for confirming sulfate ester groups in fucoidans and ulvans, and for distinguishing agar, carrageenan, and alginate types [60].

Ultraviolet–Visible (UV–Vis) Spectroscopy

UV–Vis spectroscopy supports the quantification of pigments (e.g., fucoxanthin, chlorophylls, carotenoids) and MAAs, which exhibit characteristic absorption maxima. It is frequently used as a complementary method to HPLC for pigment profiling [61].

Mass Spectrometry (MS)

Beyond its chromatographic coupling, standalone MS and tandem MS (MS/MS) provide fragmentation patterns essential for identifying unknown metabolites. High-resolution MS enables dereplication and chemotaxonomic studies, supporting the discovery of novel bioactive compounds [59].

4.3. Advances in Metabolomics and Dereplication

Metabolomics has become a central pillar in modern marine natural-products research, enabling comprehensive profiling of seaweed metabolites and accelerating the discovery of novel bioactive compounds. Recent advances in analytical platforms, data integration, and computational workflows have significantly improved the sensitivity, resolution, and throughput of metabolite identification in macroalgae. These developments are particularly relevant for Portuguese Atlantic seaweeds, whose chemical diversity spans polysaccharides, phenolics, terpenoids, halogenated compounds, and lipids [62].

4.3.1. High-Resolution Metabolomics

High-resolution mass spectrometry (HRMS), including Orbitrap and Q-TOF systems, has transformed seaweed metabolomics by enabling accurate mass determination, isotopic pattern analysis, and MS/MS fragmentation for structural elucidation. Modern workflows integrate LC–MS/MS, GC–MS, and NMR-linked metabolomics to capture both volatile and non-volatile metabolites. These platforms support both targeted and untargeted analyses, allowing researchers to detect subtle metabolic shifts in response to environmental stressors, nutrient regimes, or biotic interactions [63].

Metabolomics has also been applied to understand the biochemical responses of plants to seaweed-derived extracts, revealing complex metabolic reprogramming and stress-mitigation pathways [64]. Such studies highlight the potential of seaweed metabolites as elicitors, biostimulants, and functional ingredients.

4.3.2. Integrated Metabolomics and Functional Genomics

Recent work emphasizes the integration of metabolomics with transcriptomics and functional genomics to elucidate biosynthetic pathways and regulatory networks. This systems-level approach enables the identification of gene–metabolite associations and supports the discovery of novel enzymes involved in halogenation, sulfation, and terpenoid biosynthesis [65]. Such integration is essential for understanding species-specific chemical traits and for guiding metabolic engineering or synthetic-biology applications.

4.3.3. Advances in Dereplication

Dereplication, the rapid identification of known metabolites to avoid rediscovery, has become a critical step in seaweed bioprospecting. Modern dereplication strategies combine:

-

HRMS/MS spectral libraries;

-

In silico fragmentation tools;

-

Molecular networking platforms (e.g., GNPS);

-

Chemotaxonomic databases.

These tools allow researchers to annotate metabolites early in the workflow, prioritize novel chemical entities, and streamline purification efforts. Advanced dereplication pipelines have been proposed specifically for seaweed extracts to accelerate the identification of bioactive compounds and guide targeted isolation [66].

4.3.4. Environmental Metabolomics

Environmental metabolomics is increasingly used to assess how seaweed respond to abiotic stressors such as heavy metals, temperature shifts, and nutrient fluctuations. HRMS-based metabolomics has revealed distinct metabolic signatures in seaweeds exposed to arsenic, demonstrating the sensitivity of metabolomics for ecotoxicological assessment and biomarker discovery [63].

To synthesize the extraction and purification strategies discussed above, we present a schematic overview of an integrated biorefinery workflow for Portuguese Atlantic seaweeds (Figure 12). This visual framework illustrates the sequential steps from biomass supply and pretreatment to extraction, fractionation, and metabolite stream separation, culminating in diverse applications across nutraceutical, cosmeceutical, pharmaceutical, and biomaterial sectors. Such biorefinery models support the valorization of seaweed biomass within sustainable blue-bioeconomy strategies.

5. Bioactivities and Mechanisms of Action

5.1. Antioxidant and Anti-Inflammatory Activities

Seaweeds are recognized as rich sources of metabolites with potent antioxidant and anti-inflammatory properties, activities that underpin many of their biotechnological applications in health-related fields. The antioxidant potential of marine macroalgae arises from a diverse array of compounds, including phlorotannins, bromophenols, carotenoids, sulfated polysaccharides, and lipophilic molecules. These metabolites act through multiple complementary mechanisms that collectively mitigate oxidative stress. Phenolic compounds, particularly phlorotannins from brown algae, exhibit strong free-radical scavenging capacity due to their high density of hydroxyl groups, which readily donate electrons to neutralize reactive oxygen species [67].

Several studies conducted along the Portuguese Atlantic coast already provide quantitative evidence of the bioactivity of local seaweed metabolites, and including such examples strengthens the discussion of biological potential. Extracts of Fucus vesiculosus collected on the northern Portuguese coast have shown strong antioxidant activity, with ethanolic fractions displaying DPPH radical-scavenging IC₅₀ values in the range of 40–60 µg·mL⁻¹, largely attributed to their high phlorotannin content [6].

Extracts from Portuguese Atlantic seaweeds provide several illustrative examples of quantifiable biological activity, with IC₅₀ values that fall within the ranges reported in the studies cited throughout this review. Sargassum muticum, a widespread invasive species along the Portuguese coast, has repeatedly shown antibacterial potential, and phenolic-rich fractions typically display inhibitory effects against Gram-positive bacteria at concentrations in the low milligram-per-milliliter range, consistent with the activity profiles described for brown-algal metabolites in Portugal [14,22,27].

Among the red algae, species such as Gelidium corneum and Gracilaria gracilis produce sulfated galactans and other secondary metabolites associated with antioxidant and cytotoxic properties, and extracts from these taxa commonly exhibit ABTS or DPPH radical-scavenging IC₅₀ values within the low-to-mid hundreds of micrograms per milliliter, in agreement with the ranges reported for Rhodophyta in the Portuguese context [2,15,24,26].

Green algae also contribute relevant examples: Codium tomentosum, a characteristic species of the central and northern Portuguese coast, contains bioactive lipids and sulfated heteropolysaccharides that have been linked to anti-inflammatory and immunomodulatory effects, with inhibitory activity on nitric-oxide production typically occurring at concentrations around one hundred micrograms per milliliter, as reflected in studies addressing Chlorophyta bioactivities [17,19,20]. Together, these cases demonstrate that Portuguese seaweeds yield extracts with measurable biological effects and IC₅₀ values within the ranges expected for phenolic-, polysaccharide-, and lipid-rich fractions, reinforcing their importance as regional sources of antioxidant, antimicrobial, anti-inflammatory, and cytotoxic agents.

In addition to direct scavenging, many seaweed polyphenols chelate transition metals such as iron and copper, thereby reducing their participation in Fenton-type reactions that generate highly reactive radicals [68]. Seaweed extracts have also been shown to enhance endogenous antioxidant defenses by upregulating key enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, contributing to cellular resilience under oxidative conditions [69]. Lipophilic constituents, including Omega-3 fatty acids and carotenoids, further protect cellular membranes by inhibiting lipid peroxidation, a process central to oxidative damage in biological systems [70].

The anti-inflammatory activity of seaweed metabolites is equally significant and involves modulation of several molecular pathways associated with inflammation. Extracts from brown and red algae have been shown to suppress the production of pro-inflammatory mediators such as nitric oxide, prostaglandins, and cytokines including TNF-α, IL-1β, and IL-6, largely through the downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) [68]. Polyphenols such as phlorotannins and bromophenols also inhibit the activation of NF-κB and MAPK signaling pathways, which are central regulators of inflammatory gene expression and immune responses [67]. Sulfated polysaccharides, including fucoidans and ulvans, contribute additional anti-inflammatory effects by modulating immune cell activity, stabilizing cell membranes, and reducing leukocyte infiltration into inflamed tissues [71]. Seaweed-derived lipids, particularly EPA and DHA, further support the resolution of inflammation by serving as precursors for specialized pro-resolving mediators that actively terminate inflammatory processes [70].

Together, these antioxidant and anti-inflammatory mechanisms highlight the therapeutic relevance of seaweed metabolites and support their growing use in nutraceutical, cosmeceutical, and pharmaceutical applications. Their multifunctional bioactivity positions Portuguese Atlantic seaweeds as valuable resources for developing natural products aimed at mitigating oxidative stress, chronic inflammation, and related metabolic and degenerative disorders.

5.2. Antimicrobial and Antiviral Activities

Macroalgae produces a wide range of secondary metabolites with documented antimicrobial and, in some cases, antiviral properties. Early reviews already highlighted that red, brown, and green seaweeds contain halogenated compounds, phenolics, terpenoids, fatty acids, and sulfated polysaccharides with activity against bacteria, fungi, and viruses, underlining their medicinal and pharmaceutical potential [72]. Experimental studies have confirmed that several red algae exhibit strong antibacterial effects: extracts of Osmundea pinnatifida inhibited multiple Gram-positive and Gram-negative bacteria in vitro [73], while Pterocladiella capillacea showed significant activity against marine and human pathogenic strains [74]. These results support the view that halogenated and phenolic metabolites from Rhodophyta play an important role in chemical defense and represent promising leads for antimicrobial development [72].

Brown algae also contribute substantially to the antimicrobial repertoire. Halopteris scoparia has been shown to possess both antioxidant and antimicrobial activities, with methanolic extracts inhibiting the growth of several bacterial species, an effect attributed to phenolic and other secondary metabolites [75]. Species of Dictyopteris produce a variety of terpenoids and volatile compounds, some of which display antimicrobial and antifouling properties, suggesting ecological roles in defense and potential applications in controlling biofouling and microbial contamination [76]. Green algae have likewise been recognized as important sources of antibacterial compounds: screening of cultivated seaweed demonstrated that extracts from genera such as Ulva, Cladophora, and Chaetomorpha (Chlorophyta) inhibit fish pathogenic bacteria, indicating their potential use as natural antimicrobial agents in aquaculture [77]. Complementary work showed that several seaweed extracts, including those from green and brown taxa, are active against multidrug-resistant human pathogens, reinforcing their relevance as reservoirs of novel antimicrobial molecules [78].

The antiviral potential of seaweed is closely associated with sulfated polysaccharides. A comprehensive review of sulfated polysaccharides from marine algae demonstrated that fucoidans, carrageenans, and related polymers can inhibit viral infection by blocking adsorption and entry, interfering with viral envelope proteins, and modulating host responses [79]. These effects are strongly influenced by structural features such as degree of sulfation, molecular weight, and monosaccharide composition. Together, these studies provide solid experimental and mechanistic evidence that macroalgae are valuable sources of antimicrobial and antiviral compounds, and they support the exploration of Atlantic seaweeds, including Portuguese taxa, as candidates for pharmaceutical, aquaculture, and antifouling applications [72,73,75,76,77,78,79].

Numerous studies have demonstrated that extracts and purified compounds from Rhodophyta, Phaeophyceae, and Chlorophyta exhibit broad spectrum antimicrobial activity, often associated with halogenated compounds, phlorotannins, terpenoids, fatty acids, and sulfated polysaccharides. These metabolites act through multiple mechanisms, including disruption of microbial membranes, inhibition of essential enzymatic pathways, interference with quorum sensing, and suppression of biofilm formation [21,23]. Species such as A. armata (Rhodophyta), F. spiralis, S. muticum (Phaeophyceae), and C. tomentosum (Chlorophyta) have shown particularly strong antibacterial and antifungal activities, reinforcing their potential as natural sources of antimicrobial agents with relevance for pharmaceutical and food preservation applications [2,14].

Antiviral activity is another prominent feature of several macroalgal metabolites, especially sulfated polysaccharides such as fucoidans, carrageenans, and ulvans. These compounds inhibit viral infection primarily by blocking viral adsorption and entry, binding to viral envelope proteins, or interfering with host cell receptor interactions [27,34]. Additional mechanisms include inhibition of viral replication enzymes and modulation of host immune responses. Fucoidans from F. vesiculosus and F. spiralis (Phaeophyceae), carrageenans from Gigartina pistillata (Figure 13) and Mastocarpus stellatus (Rhodophyta), and ulvans from Ulva rigida (Chlorophyta) have demonstrated activity against a range of enveloped and non-enveloped viruses, highlighting their potential for development as antiviral coatings, prophylactic agents, and functional ingredients in health-related formulations [5,6].

5.3. Antitumoral and Cytotoxic Activities

Seaweeds from the Portuguese Atlantic coast continue to attract growing scientific interest due to their rich repertoire of metabolites with potent antitumoral and cytotoxic properties. Recent studies have highlighted the relevance of phlorotannins, meroditerpenoids, linear diterpenes, carotenoids, brominated metabolites, and sulfated polysaccharides as promising anticancer agents. These compounds act through diverse mechanisms, including apoptosis induction, oxidative stress modulation, cell-cycle arrest, inhibition of angiogenesis, and suppression of metastatic pathways [79,80].

Phlorotannins remain among the most extensively studied antitumoral metabolites in brown algae. New evidence demonstrates that phlorotannin-rich extracts from Fucus vesiculosus, F. spiralis, and S. muticum induce apoptosis via mitochondrial depolarization, caspase-3 activation, and downregulation of anti-apoptotic proteins [81]. These compounds also inhibit proliferation by arresting the cell cycle at G0/G1 or G2/M phases and reducing ROS-mediated signaling pathways associated with tumor progression [81]. Their selective cytotoxicity toward cancer cells, combined with low toxicity in non-malignant cells, reinforces their potential for therapeutic development.

Meroditerpenoids from Ericaria and Gongolaria species have also received renewed attention. Recent chemical and pharmacological studies have confirmed that compounds such as cystoseirols, chromenes, and hydroquinones exhibit strong cytotoxicity against breast, colon, and melanoma cell lines, acting through oxidative stress induction, inhibition of angiogenic mediators, and suppression of matrix metalloproteinases involved in metastasis [82]. These metabolites also display antifouling and antioxidant properties, reflecting their multifunctional ecological roles.

Linear diterpenes from B. bifurcata continue to be recognized as some of the most potent antitumoral compounds in northeastern Atlantic brown algae. Recent work has shown that eleganolone, eleganonal, and related diterpenoids inhibit cancer cell proliferation by modulating MAPK and PI3K/Akt pathways, inducing apoptosis, and generating controlled oxidative stress [83]. The abundance of B. bifurcata along the Portuguese coast makes it a particularly valuable species for sustainable bioprospecting.

Fucoxanthin, the major carotenoid of brown algae such as S. muticum, F. vesiculosus, and Gongolaria baccata, remains one of the most promising marine-derived anticancer molecules. Recent studies have demonstrated its ability to inhibit angiogenesis, suppress inflammatory mediators, induce apoptosis, and modulate autophagy in cancer cells [84]. Fucoxanthin’s low toxicity and multifunctional bioactivity have stimulated interest in its incorporation into nutraceuticals and functional foods.

Sulfated polysaccharides, particularly fucoidans from Fucus spp. and Sargassum spp., continue to show strong antitumoral potential. Recent research highlights their ability to inhibit tumor-induced angiogenesis, enhance immune responses, and sensitize cancer cells to chemotherapeutic agents [85,86,87]. Structural features such as sulfate content, molecular weight, and monosaccharide composition strongly influence their biological activity, and Portuguese populations of Fucus and Sargassum have shown particularly promising profiles.

Collectively, these recent findings reinforce the importance of Portuguese Atlantic seaweeds as reservoirs of structurally diverse metabolites with significant antitumoral and cytotoxic potential. Their ecological abundance, chemical richness, and demonstrated bioactivity position them as strategic resources for pharmaceutical innovation, functional food development, and blue-bioeconomy growth.

5.4. Antifouling and Ecologically Relevant Activities

Seaweed plays a central ecological role in coastal ecosystems by regulating interactions with epibionts, competitors, and associated microbiota. One of the most important ecological functions of macroalgal secondary metabolites is antifouling activity, which prevents the settlement of bacteria, microalgae, fungi, and invertebrate larvae on algal surfaces. Biofouling can impair photosynthesis, increase drag, reduce nutrient uptake, and facilitate pathogen entry; therefore, many macroalgae have evolved sophisticated chemical and structural defenses to maintain clean thalli [88].

Recent studies have shown that macroalgae produce a wide range of antifouling metabolites, including terpenoids, phenolics, halogenated compounds, and fatty-acid derivatives, which inhibit settlement or growth of fouling organisms. These compounds act through multiple mechanisms, such as disrupting bacterial quorum sensing, inhibiting biofilm formation, or directly impairing larval adhesion [89]. Brown algae, particularly species of Sargassum, Dictyota, Ericaria, and Gongolaria, are known to synthesize potent antifouling terpenoids, while red algae such as Asparagopsis produce halogenated metabolites with strong antimicrobial and antifouling effects, and recent work has highlighted glycoglycerolipids from Sargassum vulgare (Figure 14) as new promising antifouling agents.

Macroalgal antifouling strategies are not limited to chemical defenses. Many species also exhibit surface-mediated antifouling, including micro- and nano-scale surface textures that reduce settlement efficiency. Recent work demonstrates that seaweeds possess tightly packed, needle-like surface structures and mucilage layers that physically hinder microbial adhesion and epibiont colonization. These structural traits complement chemical defenses and contribute to the ecological success of canopy-forming species in high-energy coastal environments [90].

The antifouling activity of macroalgae is also tightly linked to ecologically relevant interactions, including allelopathy and autotoxicity. Seaweeds release metabolites that inhibit the settlement or growth of competing algae, thereby maintaining space on rocky substrates. New evidence shows that some species produce allelopathic compounds that suppress neighboring macroalgae or microalgae, influencing community structure and competitive dynamics [91]. These allelopathic interactions are particularly important in dense algal assemblages, where competition for light and substrate is intense.

Environmental conditions can modulate antifouling activity. For example, ocean acidification and pH fluctuations may alter the chemical stability and ecological function of antifouling metabolites. Modeling studies predict that future pH scenarios could affect the efficacy of macroalgal chemical defenses, potentially reshaping species interactions and fouling pressure in coastal ecosystems [92].

Beyond their ecological roles, macroalgal antifouling compounds have attracted interest in biotechnological applications, particularly as environmentally friendly alternatives to toxic synthetic antifouling paints. Extracts from species such as Ulva, Asparagopsis, and Padina have shown promising antifouling activity in laboratories and field assays, supporting their potential use in marine coatings [93]. These natural antifoulants align with global efforts to reduce the environmental impact of copper-based and biocide-rich antifouling systems.

Overall, antifouling and ecologically relevant activities represent key functional dimensions of macroalgal secondary metabolism. Through a combination of chemical defenses, structural adaptations, and allelopathic interactions, seaweeds maintain clean surfaces, regulate microbial communities, and shape the ecological dynamics of coastal habitats. These traits not only contribute to their evolutionary success but also offer valuable opportunities for sustainable biotechnological innovation.

Although many metabolites from Portuguese Atlantic seaweeds demonstrate strong bioactivities, their potential applications must also consider toxicological aspects. Certain halogenated compounds produced by red algae such as Asparagopsis may exhibit cytotoxic or irritant effects at high concentrations, while brown-algal species rich in iodine or phlorotannins can show dose-dependent physiological impacts. The biological activity of sulfated polysaccharides, including fucoidans and galactans, is also influenced by molecular weight and degree of sulfation, which may affect biocompatibility. These considerations highlight the importance of evaluating both efficacy and safety when advancing seaweed-derived metabolites toward biotechnological use [15,21,24,26,28,31,32,33,34].

6. Applications and Biotechnological Potential

6.1. Pharmaceuticals and Drug Leads

Seaweed is increasingly recognized as a strategic reservoir of structurally diverse metabolites with high potential for pharmaceutical innovation. Their unique ecological and evolutionary history has resulted in the biosynthesis of compounds not commonly found in terrestrial organisms, including sulfated polysaccharides, phlorotannins, terpenoids, halogenated metabolites, peptides, and carotenoids. These molecules exhibit a broad spectrum of bioactivities, in particular, antioxidant, anti-inflammatory, antimicrobial, antiviral, antitumoral, neuroprotective, and anticoagulant properties, making macroalgae a valuable source of drug leads for multiple therapeutic areas [94,95].

Recent advances in marine natural products research have highlighted the pharmaceutical relevance of seaweed-derived compounds. Sulfated polysaccharides such as fucoidans, carrageenans, and ulvans have demonstrated immunomodulatory, antiviral, anticoagulant, and anticancer properties, with several undergoing preclinical evaluation for applications in oncology, wound healing, and infectious disease management [95]. Fucoidans, in particular, have attracted attention due to their ability to modulate immune responses, inhibit tumor angiogenesis, and enhance the efficacy of chemotherapeutic agents.

Polyphenolic compounds, especially phlorotannins from brown algae, are promising candidates for anti-inflammatory and neuroprotective drug development. Their strong antioxidant capacity, combined with the ability to modulate key signaling pathways such as NF-κB and MAPK, positions them as potential leads for treating chronic inflammatory diseases, neurodegenerative disorders, and metabolic syndromes [94]. Phlorotannins also exhibit antimicrobial and antiviral activities, reinforcing their multifunctional pharmaceutical potential.

Terpenoids and halogenated metabolites from genera such as Dictyota, Bifurcaria, Asparagopsis, and Laurencia/Osmundea continue to be among the most pharmacologically potent seaweed-derived compounds. These molecules display cytotoxic, antifouling, antimicrobial, and anti-inflammatory activities, and several have shown selective anticancer effects in vitro. Their structural complexity and chemical novelty make them attractive scaffolds for synthetic modification and drug optimization [95].

The pharmaceutical potential of seaweed extends beyond bioactivity. Recent work emphasizes their role in sustainable drug manufacturing, as seaweed biomass can serve as a renewable source of bioactive molecules, biopolymers, and green solvents, contributing to environmentally responsible pharmaceutical production [96]. This aligns with global efforts to reduce the ecological footprint of drug development and supports the integration of marine resources into circular bioeconomy strategies.

Overall, the chemical diversity, ecological relevance, and demonstrated bioactivity of Portuguese Atlantic seaweeds position them as a valuable natural resource for pharmaceutical discovery. Continued investment in metabolomics, bioprospecting, and structure–activity relationship studies will be essential to fully unlock their potential as sources of next-generation drug leads.

6.2. Nutraceuticals and Functional Foods

Seaweeds from the Portuguese Atlantic coast constitute a valuable resource for the development of nutraceuticals and functional foods, owing to their exceptional biochemical richness and ecological adaptability. The influence of the Iberian Coastal Upwelling System, combined with the region’s biogeographic complexity, enhances nutrient availability and stimulates the synthesis of structurally diverse metabolites with recognized health-promoting properties [9,97]. As a result, Portuguese macroalgae provide an abundant source of bioactive compounds suitable for incorporation into dietary supplements, fortified foods, and functional ingredients.

Portuguese seaweeds are naturally rich in essential micronutrients, including iodine, iron, calcium, magnesium, and vitamins A, C, E, and several B-complex vitamins, making them highly attractive for nutritional applications. Species such as Fucus vesiculosus, Ulva rigida, Codium tomentosum, and Porphyra/Neopyropia spp. exhibit balanced macronutrient profiles and high antioxidant capacity, largely due to their content of phenolics, carotenoids, and sulfated polysaccharides [95]. Notably, C. tomentosum (Figure 15) shows particularly high phenolic levels, including substantial total phenolics and flavonoids, which significantly enhance their antioxidant potential and support their value as a functional food resource. Dietary fibers, particularly soluble fibers such as ulvans, agarans, carrageenans, and porphyrans, contribute to improved gastrointestinal function, glycemic control, and lipid metabolism, reinforcing the potential of these species as functional food ingredients [14,26].

Lipophilic fractions of Portuguese seaweeds also provide significant quantities of polyunsaturated fatty acids (PUFAs), including precursors of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These compounds, abundant in S. muticum, Codium spp., and Ulva spp., are associated with anti-inflammatory, cardioprotective, and neuroprotective effects [6]. Their presence enhances the nutritional value of seaweed-derived ingredients and supports their use in formulations targeting cardiovascular and metabolic health.

Beyond their nutritional composition, Portuguese seaweeds contain a wide range of secondary metabolites with demonstrated nutraceutical potential. Phlorotannins from Fucus, Ericaria, and Gongolaria spp. exhibit strong antioxidant, anti-inflammatory, and anti-diabetic activities, making them promising candidates for supplements aimed at mitigating oxidative stress and metabolic disorders [22,31]. Fucoxanthin (se Figure 12), a major carotenoid in Sargassum, Fucus, and Gongolaria spp., has been extensively studied for its anti-obesity, anti-diabetic, and hepatoprotective properties, positioning it as one of the most valuable marine-derived compounds for functional food development [28]. Sulfated polysaccharides such as fucoidans, ulvans, and galactans exhibit immunomodulatory, antiviral, anticoagulant, and prebiotic effects, supporting their incorporation into gut-health formulations and immune-support products [33,34]. Mycosporine-like amino acids (MAAs), particularly abundant in Porphyra/Neopyropia spp., provide antioxidant and photoprotective benefits, with potential applications in functional beverages and anti-aging supplements [26].

Seaweeds also hold cultural and culinary significance in Portugal, where species such as Ulva, Codium, and Porphyra/Neopyyropia have long been consumed in coastal communities. In recent years, the growing interest in plant-based diets and sustainable protein sources has stimulated the incorporation of Portuguese macroalgae into a wide range of food products, including fortified breads, pastas, snacks, fermented foods, condiments, and plant-based seafood analogs [16]. The mild, slightly saline flavor of Codium tomentosum and the high protein content of Porphyra/Neopyropia spp. make them particularly suitable for gastronomic innovation and high-value food applications.

Technological advances have further expanded the potential of Portuguese seaweeds in the nutraceutical sector. Green extraction methods, including supercritical CO₂ extraction, membrane filtration, and aqueous or ethanol-based processes, have improved the recovery of high-purity bioactive compounds while reducing environmental impact [1]. These innovations support the development of standardized ingredients with consistent bioactivity, facilitating their integration into commercial nutraceutical formulations. Additionally, Portugal’s expanding blue bioeconomy, supported by national and European initiatives, provides a favorable framework for scaling seaweed-based production and strengthening the value chain from biomass cultivation to final product development [96].

Despite their potential, several challenges must be addressed to fully realize the nutraceutical value of Portuguese seaweeds. Variability in metabolite composition due to environmental fluctuations, the need for standardized cultivation and harvesting protocols, regulatory constraints related to novel food approval in the European Union, and limited industrial-scale processing infrastructure remain significant barriers [3]. Future research should prioritize metabolomics-guided bioprospecting, optimization of aquaculture systems, including integrated multi-trophic aquaculture (IMTA) and offshore cultivation, and clinical validation of health claims. Strengthening interdisciplinary collaboration between phycology, biotechnology, nutrition science, and industry will be essential for unlocking the full nutraceutical potential of Portuguese Atlantic seaweeds.

6.3. Cosmeceuticals and Dermal Protection

Seaweeds from the Portuguese Atlantic coast represent a rich and underexploited source of bioactive compounds with significant potential for cosmeceutical applications, particularly in formulations aimed at dermal protection, anti-aging, photoprotection, and skin barrier enhancement. The harsh environmental conditions experienced by intertidal and subtidal macroalgae, such as high solar irradiance, desiccation, oxidative stress, and herbivory, have driven the evolution of sophisticated chemical defense systems. Many of these metabolites exhibit strong antioxidant, anti-inflammatory, photoprotective, and anti-melanogenic properties, making them highly attractive for incorporation into topical skincare products [28,95].

Among the most promising seaweed-derived compounds for dermal protection are phlorotannins, polyphenolic metabolites unique to brown algae. Species such as F. vesiculosus, F. spiralis, Ericaria spp., and Gongolaria spp., abundant along the Portuguese coast, produce phlorotannins with potent free-radical scavenging capacity and strong UV-absorbing properties [23,32]. These compounds inhibit matrix metalloproteinases (MMPs), reduce UV-induced oxidative damage, and modulate inflammatory pathways, thereby contributing to anti-aging and anti-photoaging effects. Their ability to chelate metal ions and protect cellular components from oxidative stress further enhances their relevance for dermal formulations targeting environmental stressors.

Mycosporine-like amino acids (MAAs), particularly shinorine, porphyra-334, and palythine, are another key group of photoprotective metabolites with strong cosmeceutical potential. These compounds, abundant in red alga such as Neopyropia leucosticta (Figure 16) and Asparagopsis spp., act as natural UV filters by absorbing UVA and UVB radiation while exhibiting antioxidant and anti-inflammatory activities [26]. Their high photostability and water solubility make them promising candidates for eco-friendly sunscreen formulations, especially in the context of increasing regulatory restrictions on synthetic UV filters due to environmental concerns.

Sulfated polysaccharides, including fucoidans, ulvans, and galactans, also contribute to dermal protection through their moisturizing, anti-inflammatory, and wound-healing properties. Fucoidans from Fucus spp. and S. muticum have demonstrated the ability to stimulate collagen synthesis, inhibit elastase activity, and promote skin regeneration, supporting their use in anti-aging and skin-repair formulations [14,34]. Their capacity to modulate immune responses and reduce erythema further enhances their value in products designed for sensitive or inflamed skin.

Carotenoids, particularly fucoxanthin, are another class of compounds with strong dermal benefits. Fucoxanthin (see Figure 12), abundant in Sargassum, Fucus, and Gongolaria spp., exhibits antioxidant, anti-inflammatory, and anti-melanogenic activities, making it suitable for formulations targeting hyperpigmentation, oxidative stress, and photoaging [28]. Its ability to modulate melanogenesis pathways and protect against UV-induced DNA damage reinforces its relevance for skin-brightening and photoprotective products.

Advances in extraction technologies, including green extraction methods such as supercritical CO₂ extraction and membrane-based purification, have improved the recovery of high-purity bioactive compounds from Portuguese seaweeds while maintaining their structural integrity and bioactivity [1]. These innovations support the development of standardized, sustainable, and high-value cosmeceutical ingredients that align with consumer demand for natural and environmentally responsible skincare solutions.

Overall, the chemical diversity and ecological resilience of Portuguese Atlantic seaweeds position them as a promising resource for the development of next-generation cosmeceuticals. Their multifunctional bioactivities, spanning photoprotection, antioxidant defense, anti-inflammatory action, and skin regeneration, offer significant opportunities for innovation in dermal protection and skincare biotechnology. Continued research into structure, function relationships, bioavailability, and formulation compatibility will be essential to fully harness the cosmeceutical potential of these marine resources.

6.4. Biomaterials and Sustainable Packaging

Seaweeds from the Portuguese Atlantic coast offer significant potential for the development of biomaterials and sustainable packaging solutions, driven by their abundance, rapid growth rates, and rich composition of structurally versatile polysaccharides. As global demand increases for biodegradable alternatives to petroleum-derived plastics, macroalgal biopolymers, particularly alginates, agarans, carrageenans, fucoidans, ulvans, and cellulose-like fibers, have emerged as promising candidates for eco-friendly materials with tunable physicochemical properties [98]. The chemical diversity of Portuguese seaweeds, shaped by strong upwelling regimes and environmental gradients, provides a valuable resource for producing high-performance biopolymers suitable for packaging, coatings, films, and composite materials.

Brown algae such as Fucus, Sargassum, Ericaria, and Gongolaria spp. are particularly rich in alginates and sulfated fucans, which exhibit excellent film-forming capacity, mechanical strength, and biodegradability. Recent studies have demonstrated that alginate-based films reinforced with seaweed-derived cellulose nanofibers or natural antioxidants can significantly improve tensile strength, barrier properties, and oxidative stability, making them suitable for food packaging applications [99,100]. The incorporation of phlorotannins or fucoxanthin into alginate matrices further enhances UV-blocking and antimicrobial properties, offering multifunctional packaging solutions aligned with circular economy principles.

Red algae, including Gelidium, Gracilaria, and Porphyra/Neopyropia spp., provide agar and carrageenan, two polysaccharides widely used in biodegradable films and hydrogels. Agar-based films exhibit high transparency, good oxygen-barrier properties, and compatibility with bioactive additives, while carrageenan-based materials offer flexibility and strong gelation capacity. Recent advances in nanocomposite engineering, such as the integration of nano-clays, chitosan, or plant-derived polyphenols, have improved the mechanical and antimicrobial performance of red-algal biopolymer films, expanding their potential for active and intelligent packaging systems [101,102].

Green algae such as Ulva and Codium spp., abundant along the Portuguese coast, are increasingly recognized for their ulvan-rich cell walls. Ulvans possess unique rhamnose-rich sulfated structures that confer excellent film-forming ability, antioxidant activity, and compatibility with biodegradable polymer blends. Ulvan-based films and coatings have shown promise for food preservation, edible packaging, and biomedical applications due to their biocompatibility and tunable mechanical properties [103,104]. Their natural green pigments and antioxidant capacity also support their use in photoprotective or antimicrobial packaging.

Beyond films and coatings, seaweed biomass is being explored for bioplastics, foams, and molded composites. Mechanical processing of whole macroalgal biomass, combined with plasticizers and natural fibers, has yielded biodegradable materials with reduced carbon footprints and competitive performance compared to conventional plastics [105]. Seaweed-based bioplastics offer advantages such as rapid biodegradation, low toxicity, and the possibility of valorizing invasive species like S. muticum, which is increasingly abundant along the Portuguese coast.

The integration of seaweed biopolymers into sustainable packaging value chains aligns with European strategies for plastic reduction and bioeconomy development. Portugal’s extensive coastline, combined with emerging seaweed aquaculture initiatives, positions the country to contribute meaningfully to the production of marine-derived biomaterials. Continued research into extraction optimization, polymer modification, nanocomposite engineering, and life-cycle assessment will be essential to fully realize the potential of Portuguese seaweeds as renewable feedstocks for next-generation sustainable packaging [95].

6.5. Opportunities for Portuguese Blue Bioeconomy Development

Portugal is uniquely positioned to expand its blue bioeconomy through the sustainable exploitation of seaweed-derived metabolites, supported by one of the most biodiverse and productive marine regions in Europe. The Portuguese Atlantic coast, influenced by the Iberian Coastal Upwelling System and the convergence of temperate and subtropical biogeographic provinces, sustains a rich macroalgal flora that includes metabolite-rich species of Rhodophyta, Phaeophyceae, and Chlorophyta [2,7]. This ecological and chemical diversity provides a strong foundation for developing high-value biotechnological applications aligned with national and European strategies for sustainable marine resource use.

The chemical richness of Portuguese seaweeds, particularly their halogenated compounds, phlorotannins, sulfated polysaccharides, terpenoids, carotenoids, and bioactive lipids, creates significant opportunities for innovation in pharmaceuticals, nutraceuticals, cosmeceuticals, and biomaterials [6,23]. Many of these compounds exhibit potent antioxidant, anti-inflammatory, antiviral, antimicrobial, and antitumoral activities, making them attractive candidates for drug discovery and functional ingredient development [4,95]. Species such as Asparagopsis armata, Gelidium corneum, Fucus spiralis, Codium tomentosum, and Sargassum muticum have already demonstrated strong bioactivity profiles, reinforcing their potential as strategic biomass resources for the Portuguese bioeconomy [2,14].

Portugal’s scientific and technological landscape further enhances these opportunities. The country hosts several marine research centers and innovation clusters with expertise in phycology, metabolomics, aquaculture, and bioprocess engineering, enabling the transition from laboratory-scale discovery to industrial-scale production. Advances in extraction technologies, green chemistry, and marine biorefinery concepts support the valorization of seaweed biomass into multiple product streams, increasing economic viability and reducing waste. The presence of established industries, such as the agar sector based on G. corneum, provides a strong industrial base for expanding into new biomaterial and biopolymer markets [15,106].

High-value sectors stand to benefit significantly from Portuguese seaweed metabolites. In pharmaceuticals, halogenated compounds from Asparagopsis, diterpenoids from Bifurcaria bifurcata, and sulfated galactans from Gracilaria spp. offer promising leads for antiviral, anticancer, and anti-inflammatory drug development [21,26]. In nutraceuticals, bioactive lipids and polysaccharides from Fucus, Ulva, and Codium species exhibit cardioprotective, immunomodulatory, and antioxidant properties, supporting their use in functional foods and dietary supplements [6,19]. Cosmeceutical applications are equally promising, with MAAs from Porphyra/Neopyropia, phlorotannins from Fucus and Ericaria, and fucoxanthin from Sargassum and Gongolaria offering natural photoprotective and anti-aging properties [26,32].

Seaweed-derived polysaccharides also present opportunities for sustainable biomaterials and circular economy solutions. Agar, carrageenan, ulvans, and fucoidans can be used to produce biodegradable films, hydrogels, and bio-based packaging materials, contributing to the reduction in petroleum-based plastics and aligning with European Green Deal objectives [34]. The valorization of invasive species such as S. muticum and A. armata offers dual benefits: mitigating ecological impacts while generating biomass for biorefinery applications.

To fully realize these opportunities, Portugal can strengthen its blue bioeconomy through targeted investments in sustainable seaweed aquaculture, offshore cultivation technologies, and IMTA systems [107]. Regulatory frameworks that support innovation, ensure environmental protection, and promote traceability will be essential. Collaboration between academia, industry, and policymakers can accelerate technology transfer and foster the emergence of startups and SMEs specializing in marine biotechnology [108]. By leveraging its natural marine capital, scientific expertise, and strategic policy environment, Portugal is well positioned to become a European leader in seaweed-based biotechnological innovation and sustainable blue-economy development.

7. Challenges and Future Directions

The growing interest in bioactive metabolites from Portuguese Atlantic seaweeds presents significant opportunities for biotechnology and blue-bioeconomy development, yet several challenges must be addressed to fully unlock this potential. One of the most pressing needs is the establishment of standardized extraction and bioassay protocols [106]. Current methodologies vary widely across studies, making it difficult to compare results, reproduce findings, or evaluate the true biotechnological value of specific metabolites. Differences in solvent systems, extraction times, purification strategies, and assay conditions can lead to inconsistent bioactivity profiles, hindering the development of robust structure–function relationships. Harmonized protocols, validated across laboratories and species, are essential for ensuring data reliability and facilitating the transition from exploratory research to industrial application [109].

Another major challenge arises from the pronounced seasonal and geographic variability in seaweed metabolite composition. Environmental factors such as temperature, light availability, nutrient regimes, hydrodynamics, and herbivory pressure strongly influence the synthesis of secondary metabolites, resulting in significant temporal and spatial fluctuations [110]. For example, phlorotannin content in brown algae, MAA concentrations in red algae, and polysaccharide sulfation patterns can vary markedly across seasons and locations. This variability complicates biomass sourcing, quality control, and industrial scaling, underscoring the need for long-term monitoring programs and predictive ecological models that can guide harvesting schedules and cultivation strategies [111].

The integration of omics tools, genomics, transcriptomics, proteomics, and metabolomics represents a critical frontier for advancing seaweed biotechnology. These approaches enable the elucidation of biosynthetic pathways, the identification of regulatory mechanisms underlying metabolite production, and the discovery of novel compounds with high biotechnological potential. Multi-omics integration can also reveal how environmental drivers shape metabolic profiles, providing insights that support strain selection, metabolic engineering, and optimized cultivation [112]. Despite their transformative potential, omics-based studies remain limited for many Portuguese seaweed species, highlighting the need for expanded genomic resources, reference databases, and interdisciplinary collaborations.

Sustainable harvesting and cultivation practices are equally essential for ensuring long-term resource availability. Wild harvesting, if unmanaged, can lead to habitat degradation, reduced biodiversity, and loss of ecosystem services. Conversely, seaweed aquaculture offers a sustainable alternative, but its development in Portugal remains in early stages. Challenges include identifying suitable cultivation sites, optimizing species-specific growth conditions, mitigating biofouling, and ensuring resilience to climate-driven stressors. IMTA and offshore cultivation systems hold promises for increasing biomass production while minimizing environmental impacts but require further technological refinement and regulatory support [113,114].

Finally, the successful commercialization of seaweed-derived metabolites depends on clear regulatory frameworks and efficient innovation pathways. Marine natural products often face complex approval processes related to safety, efficacy, environmental impact, and traceability. Inconsistent regulations across jurisdictions can slow product development and limit market access [5]. Strengthening national and European regulatory alignment, promoting certification schemes, and supporting technology-transfer mechanisms will be crucial for accelerating commercialization. Collaboration between academia, industry, and policymakers can help bridge the gap between scientific discovery and market deployment, ensuring that Portugal’s rich marine biodiversity translates into sustainable economic growth [115,116].

Together, these challenges highlight the need for coordinated research, technological innovation, and policy development. Addressing them will be essential for positioning Portugal as a leader in seaweed-based biotechnology and for realizing the full potential of its emerging blue bioeconomy.

The integration of Portuguese seaweeds into the emerging blue bioeconomy requires consideration of biomass availability, sustainability constraints, and alignment with national and EU strategic frameworks. The Portuguese coast provides abundant natural stocks of brown, red, and green macroalgae, yet sustainable exploitation depends on regulated harvesting, ecological monitoring, and the expansion of low-impact cultivation systems. Value-chain development is progressing through initiatives that link biomass supply to high-value applications in nutraceuticals, cosmeceuticals, biomaterials, and bioremediation, consistent with the priorities of the EU Bioeconomy Strategy and the Portuguese National Ocean Strategy. These frameworks emphasize circularity, carbon neutrality, and ecosystem-based management, underscoring the need to couple biotechnological innovation with responsible resource use. Strengthening these value chains will be essential for positioning Portuguese seaweeds as strategic resources within a sustainable and competitive blue bioeconomy [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67].

8. Conclusions

Despite the growing body of work on Portuguese Atlantic seaweeds, several knowledge gaps remain that constrain the full valorization of their bioactive metabolites. First, species-specific metabolomic profiles are still incomplete for many ecologically and economically relevant taxa, particularly regarding seasonal and environmental drivers of chemical variability. Second, standardized extraction, purification, and structural elucidation protocols are lacking, limiting comparability across studies and hindering scale-up. Third, toxicological and biocompatibility assessments remain scarce for most metabolite classes, especially for halogenated compounds, phlorotannins, and structurally complex polysaccharides. Fourth, biomass availability and sustainability constraints, both for wild harvesting and cultivation, require more robust ecological monitoring and life-cycle assessments. Finally, the integration of seaweed metabolites into high-value chains would benefit from coordinated efforts linking metabolomics, biotechnology, aquaculture, and blue-bioeconomy policy frameworks. Addressing these gaps will be essential for advancing the scientific, technological, and industrial potential of Portuguese seaweed resources.

Portuguese Atlantic coast hosts one of the most chemically and ecologically diverse macroalgal floras in Europe, shaped by the interplay of upwelling dynamics, biogeographic transitions, and complex ecological interactions. This environmental mosaic has driven the evolution of a rich repertoire of secondary metabolites across Rhodophyta, Phaeophyceae, and Chlorophyta, including halogenated compounds, phlorotannins, terpenoids, sulfated polysaccharides, carotenoids, MAAs, and bioactive lipids. Collectively, these metabolites exhibit a broad spectrum of biological activities, antioxidant, anti-inflammatory, antimicrobial, antiviral, antifouling, antitumoral, and cytoprotective, highlighting the exceptional biotechnological potential of Portuguese seaweeds.

Advances in green extraction technologies, chromatographic and spectroscopic methods, and high-resolution metabolomics have significantly improved the characterization of these compounds, enabling more efficient bioprospecting and accelerating the discovery of novel bioactive agents. Integrated biorefinery approaches further support the sustainable valorization of seaweed biomass, aligning with circular economy principles and reducing environmental impact.

The multifunctional properties of seaweed-derived metabolites position them as promising candidates for applications in pharmaceuticals, nutraceuticals, cosmeceuticals, biomaterials, and sustainable packaging. Their relevance extends beyond biotechnology, offering strategic opportunities for Portugal’s emerging blue bioeconomy, particularly through the development of high-value products, expansion of seaweed aquaculture, and valorization of invasive species.

Despite these opportunities, several challenges remain, including the need for standardized extraction and bioassay protocols, an improved understanding of seasonal and geographic variability, expanded genomic and metabolomic resources, and robust regulatory frameworks to support commercialization. Addressing these gaps will require coordinated efforts across research institutions, industry, and policymakers.

Overall, Portuguese Atlantic seaweeds represent a unique and underexplored reservoir of bioactive metabolites with significant ecological, scientific, and economic value. Continued investment in interdisciplinary research, sustainable cultivation, and innovation-driven bioprocessing will be essential to fully unlock their potential and consolidate Portugal’s leadership in marine biotechnology and blue-bioeconomy development.