Carotenoids in Marine Animals

Marine animals contain various carotenoids that show structural diversity. These marine animals accumulate carotenoids from foods such as algae and other animals and modify them through metabolic reactions. Many of the carotenoids present in marine animals are metabolites of β-carotene, fucoxanthin, peridinin, diatoxanthin, alloxanthin, and astaxanthin, etc. Carotenoids found in these animals provide the food chain as well as metabolic pathways. In the present review, I will describe marine animal carotenoids from natural product chemistry, metabolism, food chain, and chemosystematic viewpoints, and also describe new structural carotenoids isolated from marine animals over the last decade.


Introduction
Since the first structural elucidation of β-carotene by Kuhn andKarrer in 1928-1930, about 750 naturally occurring carotenoids had been reported as of 2004 [1]. Improvements of analytical instruments such as NMR, MS, HPLC, etc., have made it possible to perform the structural elucidation of very minor carotenoids in nature [2][3][4].
In general, animals do not synthesize carotenoids de novo, and so those found in animals are either directly accumulated from food or partly modified through metabolic reactions [5][6][7][8][9], as shown in Figure 1. The major metabolic conversions of carotenoids found in animals are oxidation, reduction, translation of double bonds, oxidative cleavage of double bonds, and cleavage of epoxy bonds.

OPEN ACCESS
Up until 2001, marine animal carotenoids were reviewed by Liaaen-Jensen [5,6], Matsuno [7,8], and Matsuno and Hirao [9]. Since then, there have been no reviews of carotenoids in marine animals. The present review describes progress in the field of carotenoids in marine animals over the last decade.

Porifera (Marine Sponges)
Characteristic carotenoids in marine sponges are shown in Figure 2. Many marine sponges are brilliantly colored due to the presence of carotenoids. Sponges are filter feeders and are frequently associated with symbionts such as microalgae or bacteria [6]. The characteristic carotenoids in sponges are aryl carotenoids such as isorenieratene (1), renieratene (2), and renierapurpurin (3) [6,7]. More than twenty aryl carotenoids have been reported in sponges [1]. Except for sea sponges, aryl carotenoids are found only in green sulfur bacteria [1,6]. Therefore, aryl carotenoids in sponges are assumed to originate from symbiotic bacteria [6,7]. Novel carotenoid sulfates having an acetylenic group, termed bastaxanthins (4), were isolated from the sea sponge Ianthella basta [1]. Recently, a new acetylenic carotenoid (5) was isolated from the marine sponge Prianos osiros [10]. Based on the structural similarity, bastaxanthins and compound 5 were assumed to be metabolites of fucoxanthin originating from microalgae.
Sea slugs and sea hares also belong to Gastropoda. They are herbivorous and feed on brown and red algae. Several apocarotenoids have been reported in sea slugs and sea hares [1]. A series of 8′-apocarotenal and 8′-apocarotenols derived from β-carotene, lutein, and zeaxanthin were found in the sea hare Aplysia kurodai [14]. They are oxidative cleavage products of the polyene chain at C-8 in C 40 skeletal carotenoids [14].
Other metabolites of fucoxanthin, crasssostreaxanthin A (35) and crassostreaxanthin B (36), were isolated from the Japanese oyster Crassostrea gigas [21]. Tode et al. demonstrated that crassostreaxanthin B could be converted from halocynthiaxanthin by bio-mimetic chemical reactions [22,23]. Further studies of carotenoids in marine animals revealed that crassostreaxanthin A, crassostreaxanthin B, and their 3-acetates were widely distributed in marine bivalves [16,17]. Moreover, two crassostreaxanthin A analogues, 37 and 38, were isolated from the oyster as minor components [16,17]. Metabolic pathways of fucoxanthin in bivalves are shown in Figure 6. .

Crassostreaxanthin A analogues
Carotenoids found in bivalves provide a key to the food chain as well as metabolic pathways. Astaxanthin and its esters were found to be major carotenoids in species of octopus and cuttlefish. Their astaxanthins consisted of three optical isomers and originated from dietary zooplankton [26].

Echinodermata (Echinoderms)
Echinenone is a well-known major carotenoid in the gonads of sea urchins and is an oxidative metabolite of β-carotene [6,7]. Echinenone from the gonads of sea urchins was found to have a 9′Z configuration (61) [29].
Recently, zeaxanthin, astaxanthin, and lutein were identified from spiny sea-star Marthasterias glacialis by HPLC-PAD-atmospheric pressure chemical ionization-MS. These carotenoids showed strong cell proliferation inhibition activity against rat basophilic leukemia RBL-2H3 cancer cell line [33].

Pisces (Fish)
Many fish accumulate carotenoids in their integuments and gonads. On the other hand, Salmonidae fish peculiarly accumulate astaxanthin (8) in muscle. Except for catfish, carotenoids in the integuments of fish exist in an esterified form.
Astaxanthin (8) is widely distributed in both marine and fresh water fish. Cyprinidae fish, which inhabit fresh water, can synthesize (3S,3′S)-astaxanthin (8a) from zeaxanthin (70) by oxidative metabolic conversion (Figure 13). On the other hand, Perciformes and Salmonidae fish cannot synthesize astaxanthin from other carotenoids [6,7,36]. Therefore, astaxanthin present in these fish originates from dietary crustacean zooplankton. Astaxanthin in these marine fish comprises three optical isomers. Perciformes and Salmoidae fish can convert astaxanthin to zeaxanthin [36,37]. Therefore, zeaxanthin in these fish also exists as three optical isomers [38].

Salmonidae fishes * Each compound consists with optical isomers
Tunaxanthin (71) is widely distributed in fish belonging to Perciformes. The bright yellow color in the fins and skin of marine fish is due to the presence of tunaxanthin. Feeding experiments involving red sea bream and yellow tail revealed that tunaxanthin (71) was metabolized from astaxanthin (8) via zeaxanthin, as shown in Figure 14 [7,36]. Carotenoids with a 3-oxo-ε-end group such as ε,ε-carotene-3,3′-dione (72) [37] are key intermediates in this metabolic conversion.

Reduction of carbonyl group at C-4/4' * Each compound consists with optical isomers
Unique apocarotenoids, micropteroxanthins (73-76), were reported from the integuments of the black bass Micropterus salmoides [39]. They were assumed to be corresponding oxidative cleavage products of tunaxanthin, lutein, and alloxanthin.

Mammalia (Mammals)
There are few reports available on carotenoids in marine mammals. Only, β-carotene and lutein were reported from the dolphin [44]. The whale is the biggest marine mammal. Whales feed on krill, which is an important dietary source of astaxanthin for marine animals. Therefore, whales might accumulate astaxanthin in the body.

Role of Carotenoids in Marine Animals and Utilization of Carotenoids for Aquaculture
Carotenoids are not essential in the nutritional sense. However, they are beneficial for animal health. It is well-known that carotenoids have an unsubstituted β-end group, such as β-carotene, α-carotene, and the β-cryptoxanthin precursor of vitamin A in animals. Furthermore, canthaxanthin was also converted to retinol in Salmoidae fish. 3-Hydroxy carotenoids: lutein, zeaxanthin, and astaxanthin, were also reported to be precursors of 3,4-dehydroretinol (Vitamin A2) in some freshwater fish [36,47].
Many marine animals accumulate carotenoids in their integuments. Integumentary carotenoids may contribute to photoprotection, camouflage, and signaling such as breeding color.
Carotenoids have excellent antioxidative activities for quenching singlet oxygen and inhibiting lipid peroxidation. Astaxanthin supplementation in Salmonidae fish suppressed oxidative stress [48,49].
Marine animals also accumulate carotenoids in their gonads. Carotenoids are assumed to be essential for reproduction in marine animals. Astaxanthin supplementation in cultured salmon and red sea bream increased ovary development, fertilization, hatching, and larval growth [50]. In the case of the sea urchin, supplementation with β-carotene, which was metabolized to echinenone, also increased reproduction and the survival of larvae [51]. Carotenoids also enhance immune activity in marine animals [52,53].
Carotenoids are used for pigmentation in several aquaculture fish. Synthetic and natural astaxanthin from Phaffia yeast and Haematococcus algae is widely used for the pigmentation of salmon, trout, and red sea bream. Lutein from marigold is also used as a yellow coloration for cultured marine fish such as yellow tail and red sea bream. Zeaxanthin from spirulina is used as a red coloration for goldfish and ornamental carp.

Conclusions
In the present review, I have described marine animal carotenoids from natural product chemistry, metabolism, food chain, and chemosystematic viewpoints and also describe new structural carotenoids isolated from marine animals during the last decade.
In plants and photosynthetic bacteria, biosynthetic roots of carotenoids were identified at the enzymatic and gene level. On the other hand, neither enzymes nor genes for the metabolism of carotenoids in animals have been clarified. Therefore, chemical, biochemical, and analytical approaches are still important to clarify carotenoids in animals.
Interesting new structural carotenoids can still be found in marine animals. The structures of these new carotenoids provide information on the function and food chain, as well as metabolic pathways in marine animals.