Astaxanthin (AX), a lipid-soluble pigment belonging to the xanthophyll carotenoids family, has recently garnered significant attention due to its unique physical properties, biochemical attributes, and physiological effects.
1O2 Generator | EDN * | EDN * | NDPO2 * | EP * | |||
---|---|---|---|---|---|---|---|
Reference | [155][156] | [156][157] | [157][158] | [158][159] | |||
Detection | Luminescence | Luminescence | Luminescence | Absorbance of DPBF | |||
Solvent | CDCl3 | CDCl3/ CD3OD (2:1) |
DMF/ CDCl3 (9:1) |
CDCl3 | CDCl3/ CD3OD (2:1) |
EtOH/CHCl3 /D2O (50:50:1) |
EtOH/CHCl3/D2O (50:50:1) |
1. Carotenoids | |||||||
Astaxanthin | 2.2 | 1.8 | 5.4 | 2.2 | 1.8 | 24.0 | 11.7 |
Canthaxanthin | 2.2 | 1.3 | 2.0 | - | 1.2 | 21.0 | |
Zeaxanthin | 2.0 | 0.73 | 3.4 | 1.9 | 0.12 | 10.0 | 11.2 |
β-Cryptoxanthin | 2.0 | 0.27 | 1.7 | - | - | 6.0 | 7.0 |
β-Carotene | 2.2 | 0.28 | 1.1 | 2.2 | 0.049 | 14.0 | 10.8 |
Lycopene | 3.0 | 1.4 | 3.4 | - | - | 31.0 | 14.0 |
Capsanthin | - | - | - | - | - | - | 12.1 |
Lutein | 0.61 | 0.26 | 2.1 | 0.8 | - | 8.0 | 8.1 |
α-Carotene | 0.66 | 0.23 | 0.93 | - | - | 19.0 | 10.0 |
Fucoxanthin | 0.29 | 0.075 | 0.97 | - | 0.005 | - | - |
Tunaxanthin | - | - | - | 0.15 | - | - | - |
2. Vitamin C | |||||||
L-Ascorbic acid | - | - | 0.00089 | - | - | - | - |
3. Vitamin E | |||||||
α-Tocopherol | 0.02 | 0.0039 | 0.049 | - | - | 0.28 | 0.13 |
β-Tocopherol | - | - | - | - | - | 0.27 | 0.093 |
γ-Tocopherol | - | - | - | - | - | 0.23 | 0.084 |
δ-Tocopherol | - | - | - | - | - | 0.16 | 0.041 |
Trolox | - | - | 0.010 | - | - | - | 0.042 |
4. Polyphenols/other phenolic antioxidants | |||||||
α-Lipoic acid | 0.056 | 0.038 | 0.072 | - | - | 0.13 | 0.0019 |
Ubiquinone-10 | 0.0019 | 0.0021 | 0.0068 | - | - | - | 0.062 |
BHT | - | - | 0.004 | - | - | - | - |
Caffeic acid | - | - | 0.0023 | - | - | - | 0.00069 |
Ferulic acid | - | - | - | - | - | - | 0.00027 |
CurcuminI | - | - | 0.0036 | - | - | - | - |
(-)-EGCG | - | - | 0.0096 | - | - | - | 0.0051 |
Gallic acid | - | - | 0.0023 | - | - | - | - |
Pyrocatechol | - | - | 0.0055 | - | - | - | - |
Pyrogallol | - | - | 0.0055 | - | - | - | - |
Quercetin | - | - | 0.0018 | - | - | - | - |
Resveratrol | - | - | 0.0018 | - | - | - | - |
Sesamin | - | - | 0.0012 | - | - | - | - |
Capsaicin | - | - | 0.0021 | - | - | - | - |
Probucol | - | - | 0.00044 | - | - | - | - |
Edaravon | - | - | 0.0067 | - | - | - | - |
Taxon | Scientific Name | Common Name | Astaxanthin | Reference | |||
---|---|---|---|---|---|---|---|
Form † | Stereoisomer (3R,3′R, meso, 3S,3′ |
Name P450 |
Origin | Super-Family, Clan | Methodlogy of Functional Analysis | Reference | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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S | ) | Content (mg/100 g) | Origin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Bacteria, Prtoteobacteria, Alphaproteobacteria | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CYP2J19 | Aves/Testudines | CYP2 | Genetics Heterologous expression Homology |
[321]][321[552],552[553][557,553,557] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Paracoccus carotinifaciens (w/. mutation) |
PanaFerd-AX | Free form | 3S,3′S | 2180 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CYP2AE2 | Zebra fish; | Danio albolineatus | (50.2% of total Car) | De novo |
CYP2 | Genetics Heterologous expression | synthesis | [556][557][556,557] | [329][330][329,330] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Paracoccus sp. strain N81106 (NBRC 101723) (Agrobacterium auranticum) (w/. mutation) |
N/A | Free form and glycoside | 3S,3′S | ~800 (63.2% of total Car) |
De novo synthesis |
[331] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Actinopterygii: Cypriniformes) | Brevundimonas sp. M7 (w/. mutation) |
N/A | Free form ** | 3S,3′ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CYP2J2 | S ** | Anole Lizards; | Anolis favillarum | 130 | CYP2 CYP2 | De novo Synthesis ** |
[186] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Genetics | [ | 313 | ] | Sphingomonas astaxanthinifaciens TDMA-17 |
N/A | Free form | 3S,3′S ** | 96.0 (34.3% of total Car) |
De novo Synthesis ** |
[182 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CYP2J6 | ] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Reptilia: Iguania, (Lepidosauria)) | Paracoccus haeundaensis KCCM 10460 (Co-culture w/. Lactic Acid Bacteria) |
N/A | Free form | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CrtS (CYP5139Q1) | 3 | S, | Phaffia Yeast; | 3′S ** | 82.1 | De novo synthesis |
Xanthophyllomyces dendrorhous | CYP3 | Heterologous expression | [212][213][558][212,213,558] | [332] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Paracoccus bogoriensis BOG6T (DSM16578, LMG2279) | N/A | Free form | 3S,3′S | 40 (10.8% of total Car) |
De novo synthesis |
[183] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Fungi: Basidiomycetes) | Brevundimonas spp. | N/A | Free form ** | 3S,3′S ** | 2.8~36.5 | De novo | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CYP384A1 | Spider mites; | Tetranychus kanzawai | Synthesis ** | CYP3 | Genetics | [375] | [186] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sphingomicrobium astaxanthinifaciens CC-AMO-30B |
N/A | Free form | 3S,3′S ** | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CYP383A1 | 4.0 | (Arthropoda: Chelicerata) | CYP3 | De novo | Synthesis ** |
[185] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Putative | (Closest homologue of CYP384A) | Brevundimonas sp. strain SD212 (NBRC 101024) |
N/A | Free form | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CYP3A80 | Sira poison Frog; | S, | 3′S | N/A | Ranitomeya sirensis
The respective number was quoted from the reference(s), and it may vary depending on the collection location and season.†, the presence of binding forms to carotenoproteins would not be mentioned in this table; ‡, the identification method of the compounds remains uncertain; *, the biosynthetic pathways have not been fully characterized; **, based on the information on close species/genus; N/A; not available; N/D; not detected.*** Since astaxanthin is diversely found in the skin, feathers, and retinas of birds, only the characteristic reports are described. ?; based on the information on close taxa. For the details of distribution in avian species, see the other review [314]. 2.3. Biosynthesis and Metabolism of Astaxanthin2.3.1. Overview of Carotenoid Biosynthetic Pathways in Bacteria, Fungi, and Higher PlantsThe biosynthesis of AX is entirely based on β-carotene as the common precursor. Therefore, this document omits a detailed discussion of the metabolic pathway to β-carotene. Briefly, carotenoids belong to isoprenoids, which are the most diverse group of natural compounds. Isoprenoids are commonly biosynthesized from isopentenyl diphosphate (IPP). IPP is synthesized via the mevalonate pathway, which is present in almost all eukaryotes (the domain Eukarya) and archaea (the domain Archaea), as well as some actinobacteria (the phylum Actinomycetota). Alternatively, the MEP (2-C-methyl-D-erythritol 4-phosphate) pathway is used, which begins with pyruvate and glyceraldehyde 3-phosphate and proceeds through 1-deoxy-D-xylulose 5-phosphate (DXP) and MEP. This pathway is found in almost all bacteria and the chloroplasts of photosynthetic eukaryotes. IPP is isomerized to dimethylallyl diphosphate (DMAPP) through the action of IPP isomerase (Idi; IDI). Subsequently, DMAPP is converted to farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) through sequential condensation reactions with IPP. These reactions are catalyzed by FPP synthase and GGPP synthase, respectively [397]. Figure 810 illustrates the biosynthetic pathway of carotenoids from FPP in the leaves of higher plants, highlighting the enzyme-catalyzed reactions involved. Additionally, this figure presents the functions of carotenoid biosynthesis enzymes derived from bacteria and fungi [154][155]. According to past reports, the group of enzymes involved in the carotenoid synthesis pathway in green algae is composed of a set of genes that share homology with those of higher plants [398].![]() Figure 810. Biosynthetic pathway of carotenoids in the leaves of higher plants. Plant-type enzymes are shown with green letters, while bacterial enzymes and fungal enzymes that can catalyze in this pathway are written in pink and red, respectively.
2.3.2. Overview of Astaxanthin Biosynthetic Pathways in Bacteria, Algae and PlantsThe β-C3-hydroxylation and β-C4-ketoxylation reactions involved in AX biosynthesis are present in a wide taxonomic range of organisms. These reactions are mainly catalyzed by membrane-integral, diiron, nonheme oxygenase superfamily enzymes, and occasionally heme-dependent cytochrome P450-type monooxygenase enzymes. Detailed information regarding these enzymes is provided below. In Proteobacteria, such as the genera Paracoccus and Brevundimonas, the genes responsible for AX biosynthesis are well understood (refer to Section 2.2.1). AX is synthesized from β-carotene through the coordinated actions of CrtZ-type β-C3-hydroxylase (β-carotene 3,3′-hydroxylase; CrtZ) (EC: 1.14.15.24) and CrtW-type β-C4-ketolase (β-carotene 4,4′-oxygenase; CrtW) (EC: 1.14.99.63; including an incorrect description on the substrate specificity) with β-carotene as the initial substrate (see Figure 78 and Figure 911) [37][399][37,399]. However, due to variations in enzyme reactivity among different species, AX-producing bacteria often accumulate significant amounts of precursors, especially adonixanthin.![]() Figure 911. Conversion routes from β-ring to 3-hydroxy-4-keto-β-ring in AX-biosynthesizing organisms. ASY, also called CrtS, from Xanthophyllomyces dendrorhous; CrtW and CrtZ, from bacteria; BKT and BHY, from green algae; CBFD and HBFD, from Adonis aestivalis.
2.3.3. How Can Hematococcus Algae Achieve Ultra-High Concentrations of Astaxanthin Biosynthesis?Haematococcus algae exhibit remarkable potential for accumulating up to 9.8% of AX in cell weight under specific culture conditions [328]. These AX compounds predominantly exist as mono- and diesters, gracefully stored within oil droplets housed in the resilient cyst cells, as discussed earlier (refer to Section 2.2.2). Notably, mature aplanospores (cysts) showcase the presence of AX primarily within intracytoplasmic oil droplets rather than plastid-derived chromoplasts [223][247][248][249][250][251] [223,247,248,249,250,251]. These specialized droplets serve a dual purpose, shielding the nucleus as antioxidants and acting as light filters, effectively reducing excitation pressure on photosynthetic subunits and mitigating the risk of photodamage [405].How is it possible for Haematococcus algae to achieve such a high concentration of AX compared to other organisms? One significant reason for this is their ability to accumulate the majority of AX as oil droplets in oil vacuoles within the cytoplasm rather than in plastids. These oil droplets, protein-lined structures typically synthesized from the endoplasmic reticulum, efficiently accumulate lipids (Figure 103), as observed in mammalian adipocytes and other organisms. Another crucial factor is the ester form of AX. Free AX, in the absence of a carrier protein, can aggregate at a certain soluble concentration, even in the presence of lipids as a solvent, potentially imposing physical stress on the cells. However, as fatty acid esters, the solubility of AX in fats, particularly triglycerides, is greatly enhanced. The biosynthesis and accumulation of AX and triglycerides within oil droplets occur in a coordinated manner, with de novo synthesis of free fatty acids and AX esterification taking place sequentially along this pathway (Figure 103) [406][407][408][409][410][406,407,408,409,410]. Consequently, Haematococcus algae have the capability to accumulate AX within oil droplets in the cytoplasm while the volume of the chloroplasts decreases.
![]() Figure 103. Pathways and localization of astaxanthin biosynthesis and esterification in Haematococcus algae. ACCase, acetyl CoA carboxylase; DGAT, diacylglycerol acyltransferase; FAS, fatty acid synthase; FA, fatty acid; SAD, stearoyl acyl carrier protein desaturase; TAG, triacylglycerol. Other enzyme abbreviations are listed in the main text. This figure was reproduced from ref. [410] with the permission of the publisher.
2.3.4. Metabolism of Astaxanthin in AnimalsOverviews of Metabolism of Astaxanthin in Animals; General RemarksIn animals, the accumulation of carotenoids, including astaxanthin (AX), is the result of complex food chains and metabolism. As depicted in Figure 114, carotenoids are biosynthesized in organisms at the beginning of the food chain. These organisms serve as prey for higher-level organisms, which selectively accumulate and metabolize carotenoids, including precursor forms and AX. Concurrently, AX can undergo metabolic processes, leading to the formation of different carotenoids or degradation. This section aims to present the most recent findings concerning the metabolism of AX in non-mammalian animals.![]() Figure 114.
Metabolic Conversion to Astaxanthin by Cytochrome P450In terrestrial animals, AX and its related “red” ketocarotenoids are commonly found in the retina and serve as ornamental coloration on the skin and plumage of reptiles and birds, as discussed in Section 2.2Section 2.2.5.5. The precise role of AX in these organisms remains hypothetical; however, it is clear that AX accumulation is derived from carotenoids present in their food through the food chain. In the case of fish, crustaceans, and flamingos, it has long been known that AX is converted from “yellow” carotenoids such as β-carotene and zeaxanthin, which can be precursors obtained from their diet. However, the specific enzymes involved in this conversion have remained unclear (Section 2.2.5). Recent studies have suggested an intriguing possibility that the red color characteristic of these organisms may also arise from the conversion of “yellow” carotenoids, such as β-carotene and zeaxanthin, by certain cytochrome P450 (CYP; P450) (refer to Table 3). The involvement of P450s in AX biosynthesis has been demonstrated through the analysis of ASY (CrtS) in Phaffia yeast, as discussed in SectionSection 2.3.1. 2.3.1. Notably, the P450s presumed to be involved in the metabolic conversion to AX in the animal kingdom are diverse and do not have direct orthologs to ASY (CrtS). In their study, Mundy et al. made a groundbreaking discovery by identifying a P450 gene (CYP2J19) that is potentially involved in the biosynthesis of “red” ketocarotenoids for the first time in the animal kingdom. They accomplished this through a comprehensive genetic analysis of the “yellowbeak” mutant of the zebra finch (Taeniopygia guttata) [552]. The yellowbeak mutant possesses a mutation in CYP2J19 within the gene cluster encoding CYP2, where the wild type exhibits CYP2J19A and CYP2J19B, whereas the yellowbeak mutant has CYP2J19yb. Consequently, CYP2J19A is exclusively expressed in the retina, while CYP2J19B is expressed in the beak and tarsus, with varying levels of expression in the retina. Conversely, CYP2J19yb expression is barely detectable in the beak of yellowbeak birds. These findings establish the essential role of CYP2J19 in ketocarotenoid biosynthesis in zebra finches [552]. Furthermore, Lopes et al., who belong to the same research group as mentioned above, reported the whole genome sequencing of red siskins (Spinus cucullata, exhibiting red body color), common canaries (Serinus canaria, exhibiting yellow body color), and “red factor” canaries (a crossbreed of red siskins and canaries) to investigate the genetic basis of red coloration in birds [553]. Their research identified two genomic regions crucial for red coloration in “red factor” canaries, one of which contains the gene encoding CYP2J19. Transcriptome analysis revealed a significant upregulation of CYP2J19 in the skin and liver of red factor canaries, further suggesting that CYP2J19 functions as a β-C4-ketolase, catalyzing the conversion of ketocarotenoids in birds [553]. It is plausible to assume that these P450 proteins acquired their functions through convergent evolution within each respective order/suborder [554]. While the metabolic pathways of these AX-generating P450s are expected to be similar to those of Phaffia yeast, information regarding the substrates involved in each P450 reaction and the absolute configuration of the resulting C3, C3′positions remains limited. The available data suggests that Acari, an organism capable of producing AX, exhibits an optical configuration of (3S,3′S), which is the opposite of the (3R,3’R) configuration observed in Phaffia yeast, as reported in an earlier publication. Therefore, it is anticipated that future studies will shed light on the reaction mechanisms, the substrate specificity of each P450 involved in AX conversion, the optical configuration of the produced AX, and the intermediates formed during the reaction. The CYP2J19 gene, generally present as a single copy in their genome, is widespread among avian lineages. This observation aligns with the notion of a conserved ancestral function in color vision, followed by subsequent co-selection for red epidermis coloration. Similar to several other CYP loci with conserved functions, CYP2J19 exhibits evidence of having undergone positive selection across bird species. Although there is no direct evidence indicating changes in selection pressure on CYP2J19 associated with co-selection for red pigment, it is possible that compensatory mutations related to selection on the adjacent gene CYP2J40 may contribute to this phenomenon [321]. In contrast, as discussed in Section 2.2.4, certain birds, such as penguins, kiwi, and some owls, lack ketocarotenoid-containing cone oil droplets in their retinas. In these avian species, the CYP2J19 gene has undergone pseudogenization [320]. Although penguins do contain AX in their body tissues, it is believed to be derived from their diet [395][396][395,396]. Interestingly, there have been reports indicating that some bird species may have lost and subsequently regained the function of CYP2J19 during the course of evolution, suggesting the potential advantageous significance of reddish body coloration and the acquisition of ketocarotenoids for birds [555]. The zebra finch, for which the function of the CYP2J19 gene was first indicated, also has two copies of the CYP2J19 gene that have probably been duplicated during evolution [552]. Among tetrapods, turtles are the only group that possesses red oil droplets in their retinas, and several turtle species exhibit red carotenoid coloration. Twyman et al. conducted a study on the evolution of CYP2J19, a gene associated with color vision and red pigmentation in reptiles, utilizing genomics and gene expression analysis. They discovered that turtles, but not crocodilians and lepidosaurs (including lizards, snakes, and tuatara), possess orthologs of CYP2J19, which originated from a gene duplication event prior to the divergence of turtles and archosaurs. CYP2J19 is strongly and specifically expressed in the retina and red outer skin of turtles, which include ketocarotenoids. The researchers propose that CYP2J19 initially played a role in the color vision of archosaurs, and they conclude that red ketocarotenoid-based coloration independently evolved in birds and turtles through genetic regulation changes involving CYP2J19. In other words, these intriguing findings suggest that red ketocarotenoids might have contributed to color vision and ornamental coloration in dinosaurs and pterosaurs [554]! Therefore, the presence of CYP2J19 genes plays a crucial role in the ketolation of carotenoids in avian and reptilian species. However, reptiles, particularly lepidosaurs, likely lack CYP2J19 [554]. Despite this, several reptile species exhibit ketocarotenoids, such as AX, in their integumentary coloration (refer to Section 2.2.4. for more details). Subsequently, a genetic approach identified genes involved in the conversion of carotenoids to ketocarotenoids in spider mites and a species of zebrafish [375][556][375,556]. Interestingly, these P450-type C4-ketolase enzymes in spider mites and zebrafish are not encoded by CYP2J19 but are shown to be associated with separate P450 enzyme genes. For instance, in spider mites (Tetranychus kanzawai), the P450 encoded by the CYP384A1 gene significantly contributes to red body coloration through ketocarotenoids [375]. Similarly, in the zebrafish species (Danio albolineatus), the CYP2AE2 gene is involved in the accumulation of red pigment in the skin erythrophores [556][557][556,557]. In other organisms, genetic studies and homology with known carotenoid oxygenases indicate the involvement of various P450 enzymes in the β-C4 oxygenation of carotenoids (Table 3). For example, Anolis favillarum, a reptile belonging to the lepidosauria (lizards), exhibits white, yellow, and orange skin. The orange skin coloration is attributed to pteridines and ketocarotenoids. As mentioned earlier, reptilian lepidosauria have lost CYP2J19 during evolution [N/D; not determined.
2.4. Chemical Synthesis and Analysis of Astaxanthin2.4.1. Chemical Synthesis of AstaxanthinIn this document, while the main focus is on AX derived from biological sources, a brief overview of chemically synthesized AX will also be provided. In 1967, Surmatis et al. were the first to synthesize AX in its dimethyl ester form [564]. I In the same year, Leftwick and Weedon successfully synthesized the free form of AX from canthaxanthin [565]. In the early 1980s, the group at Hoffman-LaRoche achieved the total synthesis of astaxanthin through the Wittig reaction of C15-end-group phosphonium salts at both ends of the central C10-dialdehyde (Figure 125). Using this method, they synthesized (3S,3′S), meso, and (3R,3′R) optical isomers of AX, along with several geometric isomers [566]. This synthetic method was employed for industrial synthesis, and synthetic AX is still commercially available as a coloring agent in aquaculture for fish such as salmon, trout, and sea bream. It is important to note that commercial products (Carophyll Pink or Lucantin Pink) are coated with gelatin and starch, making them water-dispersible.![]() Figure 125. Industrial synthesis route for astaxanthin.
2.4.2. Quantitative and Qualitative Analysis of AstaxanthinPractical analysis of AX is primarily conducted using UV/VIS absorbance spectrophotometry and/or HPLC methods. The absorbance spectrophotometric method is simple and cost-effective when analyzing samples that predominantly contain AX as the carotenoid. The molecular absorption coefficient 𝐸1%𝑐𝑚 = 2100 (in acetone, hexane, and EtOH) of AX is often utilized [4][68][4,68]. HPLC systems are commonly employed for the quantification and identification of AX in carotenoid mixtures. Reversed-phase systems using ODS or C-30 columns are frequently used for quantitative and LC-MS analysis [64][68][264][568][64,68,264,568]. However, normal-phase systems with silica gel columns or CN columns can also be employed. The normal-phase system offers superior separation efficiency for analogues with similar polarity and geometrical isomers [56][181][187][196][401][56,181,187,196,401]. Chiral columns such as Sumichiral OA-2000 can be used for the analysis of optical isomers [53]. Commercially available, highly purified AX can be used as a standard; however, if the origin of the standard is synthetic, it typically consists of a mixture of the three optical isomers, unless otherwise specified. Standard AX esters from Haematococcus algae can be purchased from the USP with validated concentrations [68]. Depending on the analytical environment, however, it has been reported that the quantitative value may not be consistent due to the influence of light and ambiguous other factors [569]. This is considered to be mainly due to the fact that 13- and 15-cis geometrical isomers, which are bent around the center of the molecule, are easily converted to all-trans isomers by light [56][147][56,148]. Therefore, it is considered necessary to standardize the conditions for quantification, such as performing the analysis under light-shielded conditions. For another reason, geometric isomers with two or more of the molecule’s double bonds arranged in the cis configuration (e.g., di-cis isomers) have not been included in the quantitative values by the current USP method. Since these “multi”-cis molecules are also affected by light, it is possible that the quantitative value is estimated to be low by the current method. Therefore, the development of an improved analytical method should accelerate in the near future. When AX presents as its fatty acid esters (See Section 2.1.2), it must be hydrolyzed by cholesterol esterase or lipase to lead to the free form for identification and/or quantification. For example, in the case of quantitative analysis of AX in Haematococcus algae, the analytical method was validated using cholesterol esterase from Pseudomonas sp. (EC 3.1.1.13, available from Merck (Sigma-Aldrich) or FUJIFILM Wako Chemicals) [68]. In some instances, an inexpensive lipase powder from Candida cylindracea (EC 3.1.1.3, Lipase OF, Meito Sangyo Co., Ltd., Japan) [265] was used for qualitative analysis, showing comparable activity to cholesterol esterase. Roche’s group employed alkali saponification under completely anoxic conditions to saponify the fatty acid esters of AX, leading to free AX; however, the experimental setup and operation were highly complex [570]. Preparative liquid separation is often required for the purification of post-saponification treatments and biological samples. In such cases, the use of an internal standard (IS) with similar physical properties is crucial. Preferred IS options include Ehinenone, Ethyl 8′-apo-β-caroten-8′-oate, and trans-β-apo-8′-carotenal [68][568][571][572][68,568,571,572]. HPLC allows for the separation of all-trans forms of AX and geometrical isomers such as 9-cis, 13-cis, and 15-cis AX. These isomers exhibit different UV-VIS spectra and can be easily identified by comparison with reference values if the HPLC system includes a PDA detector [4]. More recently, LC-MS with APCI and ESI ionization, along with UV-VIS detection, has been used for the detection of AX during separation using HPLC systems. AX exhibits a prominent protonated molecule (MH+) with m/z 597 in APCI and ESI-MS. The detection sensitivity of carotenoids by LC-APCI-MS and LC-ESI-MS has significantly improved to the sub-ng order. LC/MS (or MS/MS) is also a powerful tool for the analysis of complex mixtures such as AX fatty acid esters and AX glycosides [64][265][64,265]. While HPLC analysis is accurate and reliable, it involves complex procedures and requires skill for analysis. In recent years, the use of resonance Raman spectroscopy has been considered as a potential solution for more noninvasive, on-site analysis. The resonance Raman spectra of AX, when excited by visible lasers, exhibit dominant bands at approximately 1008 cm−1, 1158 cm−1, and 1520 cm−1 [573]. Raman spectra measured on samples of salmon fillets at fish markets have demonstrated the detection of AX in salmon skeletal muscle [129]. Portable Raman spectrometers have become available, allowing for on-site studies, and it has been reported that the signal intensity of the AX-specific Raman band at 1518 cm−1 (C=C stretching frequency) increases in an AX concentration-dependent manner. This signal can be distinguished from fish proteins and lipids, enabling the determination of AX levels in different parts of salmon fillets and different species of salmon. These findings indicate the effectiveness of Raman spectrometry for on-site AX quantification [574]. Polynomial approximation or multivariate curve resolution-alternating least squares (MCR-ALS) using the Raman spectrum has also been used for the quantification of salmon, Phaffia yeast, and Haematococcus algae [251][575][576][577][251,575,576,577]. Raman microscopy has shown great potential for diverse types of analysis. AX, due to its strong lipophilic properties, co-localizes with lipid fractions in cells and exhibits a characteristically strong Raman spectrum. Therefore, it has been investigated as a non-toxic, non-destructive Raman probe for organelles [578][579][578,579]. Pioneering studies have used resonance Raman microscopy to determine the localization of topically applied AX in skin tissue [580]. It appears that the methods mentioned in these reports can also detect analogues (such as canthaxanthin and adonirubin) and degradation products [581], although these are not major concerns when the purity of AX is relatively high and the variation in the profile of these impurities is minimal. In conclusion, the selection of an appropriate analytical method is crucial and depends on the specific requirements of the analysis.2.5. Relationship between Human Culture and Astaxanthin2.5.1. Historical Exposure of Human Societies to Astaxanthin Sources in NatureHuman societies have interacted with nature for thousands of generations and taken advantage of substances with medical and health benefits. Carotenoids are the most abundant family of pigments in nature. Aquatic resources create numerous opportunities for humans to experience various applications of natural pigments, including AX [582]. AXs namesakes, the crayfish and lobster, hold an important place in many culinary and cultural traditions, including those of Sweden and America. Astacus astacus is a European crayfish species native to Scandinavia, that become popular among Swedish nobles in the Middle Ages. By the 16th century, festive crayfish parties became a Swedish tradition, primarily featuring freshwater crayfish (flodkräfta) or marine lobster (Nephrops norvegicus) in the case of the Swedish west coast. Both crayfish and lobster turn bright red after boiling when AX is released from a protein complex in the crustaceans’ shell. The celebration was coined “kräftskiva” in the 1930s and is still celebrated to-day in the month of August [583][584][583,584]. The luxury and popularity of AX-rich crustacean meals were often depicted in the still-life paintings of the Dutch Golden Age. The bright oranges and reds of cooked crustaceans were centerpieces in paintings depicting light breakfasts called “ontbijtjes” and lavish banquets featuring objects of luxury, called “banketje” or “pronkstilleven” [584]. In the United States, the red swamp crayfish (Procambarus clarkii) is popular in the state of Louisiana, where crayfish are also known as crawfish, mudbugs, and crawdads. The crawfish is a central figure in the culture of Louisiana’s Native American Houma nation. He was once part of the Chakchiuma group, distantly related to both the Choctaw and Chickasaw. “Shâkti Humma”, or “red crawfish”, was a giant crawfish who created the world and formed living creatures out of mud. Houma warriors depicted the red crayfish as their war emblem because this tiny creature is known to brandish its pincers, never backing down, even in the face of larger enemies. The red crawfish was an integral symbol of resilience and strength, and even the word “Hou-ma” means “red” [585][586][587][585,586,587]. When the Acadians from the Canadian maritime provinces settled in the bayous of Louisiana in the 17th century, they may have observed the Houma harvesting crawfish. The Acadians, now called Cajuns, may have adapted their Canadian lobster recipes for making crawfish boils, which today form the backbone of Louisiana cuisine. In the 1980s, the crawfish officially became Louisiana’s state crustacean, further reinforcing the cultural significance of AX in this region [588]. Although crustaceans are a celebrated source of AX, the most abundant source of AX in the human diet is wild salmon. Salmon have been an important food source for coastal cultures across the Northern Hemisphere since prehistoric times and are widely featured in legends and depicted in art. The oldest known image of salmon may be a relief carving of a salmon in a cave in France from the Gravettian era (25,000–20,000 BCE) [589][590][589,590]. Salmon is revered in many parts of the world. In Native American art, salmon are a symbol of perseverance, ancestral knowledge, and spiritual journey. The First Salmon Ceremonies practiced across the American Northwest celebrate the arrival of spawning salmon each spring [591]. In Celtic mythology, Fionn mac Cumhaill, the legendary giant credited with constructing Northern Ireland’s famous Giant’s Causeway, gained knowledge of the world by tasting the Salmon of Wisdom [592]. One of the tales from the 6th century featuring King Arthur recounts his quest, during which he rode on the back of a salmon to Gloucester and freed a captive deity [593]. In Icelandic Norse mythology from the 13th century, the trickster deity Loki transformed into a salmon to escape his brother Thor. However, Thor caught Loki at the base of his tail, forming the iconic grip point for fishermen [593]. In the city of Murakami in Niigata Prefecture, Japan, salted and wind-dried salmon have been prepared using traditional methods since the Heian period (794 to 1185). The history of salmon consumption in the region can be traced back even further, with salmon bones found in archaeological remains from the Jomon era (pre-B.C.). Salmon has long been recognized as one of the most important foods in the region. During the Edo period (1603–1867), when Murakami served as a feudal domain under the Tokugawa shogunate, salmon held significant economic value, serving as a currency for paying taxes, presenting gifts to the Imperial Court and Tokugawa shogunate, and being distributed as salaries to government officials. In the late Edo period, when salmon catches in the Miomotegawa River flowing through the city declined, a samurai named Heiji Aotobu proposed a salmon propagation project to the domain government. River construction and resource conservation efforts were undertaken to create an environment conducive to salmon spawning, resulting in the recovery of salmon populations. This work was groundbreaking in terms of sustainable fishing practices. Presently, Murakami salmon continues to be presented as gifts and is featured in special meals during New Year celebrations [594]. Murakami’s salted salmon has also been used in the Daijosai, the first Niiname-sai (a Japanese harvest ritual) of a Japanese emperor following their enthronement. This once-in-a-generation festival involves the emperor serving the newly harvested grains to the gods of heaven and earth, “Amaterasu and Tenjin Chigi”, as well as partaking in them. The festival site, known as “Yuki” in the east and “Suki” in the west, receives harvested grains from all over Japan to be offered to the gods. Murakami’s salted salmon is among the products from Niigata Prefecture dedicated to Yuki [595]. The Ainu people, who have inhabited northern parts of Japan since ancient times, also consider salmon to be a vital dietary source. The Ainu refer to salmon as “kamuichep” (divine fish) or “shipe” (the true food). The Ainu hold a “new salmon prayer” called “Asiri Chep-nomi” when the salmon return, seeking a bountiful catch. They have various rituals and traditions associated with salmon, which skillfully reflect the salmon’s ecology and the wisdom of their ancestors. For example, the first salmon to return to the river is reserved for the fox gods, who protect the water source, and must not be caught. The subsequent salmon are designated for other gods and then shared among humans, who rely on the salmon for sustenance [596][597][596,597]. Moreover, salmon holds deep cultural and culinary significance not only for the Ainu but also for the indigenous peoples of the North Pacific [596]. While animal sources continue to inspire and sustain AX consumption, the increasing demand for AX as a nutritional supplement must not become a burden on aquatic ecosystems. As exemplified by samurai Heiji Aotobu, environmental conservation and stewardship must guide towards a sustainable future. That is why we turn to Haematococcus algae as a sustainable source of natural AX.2.5.2. Human Culture Shift towards Sustainability: Haematococcus algae as a Promising Source of Natural AstaxanthinAs discussed, historical evidence suggests that indigenous or traditional knowledge, such as knowledge about food and medicine, was developed through human interaction with the environment and nature. This knowledge has been passed down through generations as an integral part of human culture. In addition to aquatic animals such as shrimp and salmon, the consumption of freshwater aquatic plants has ancient origins due to their abundance, unique sensory properties, and nutritional and health benefits [598]. Microalgae and seaweed have been used as food since medieval times and have established markets in Asia, with a growing market in Europe [599]. Archaeological findings from Monte Verde, Chile, indicate that the use of marine algae as food dates back around 14,000 years [600]. Not only were aquatic plants consumed as food, but plant-based medicinal extracts, including algae, herbs, and fungi, were also prevalent. This knowledge forms the foundation for many contemporary health-related discoveries. In fact, over the past century, eating and feeding practices have evolved from social and cultural customs to explicit healthcare and medical practices [601]. Modern nutritional science has shed light on the nutritional and therapeutic effects of various components found in aquatic plants and their role in biological processes. Furthermore, it is essential not to overlook the connection between the health of human populations and the Earth’s natural food systems and biodiversity, as well as the role of microalgae in ecosystem preservation. In the late 18th century, Alexander von Humboldt, an influential German scientist, was one of the first to note the negative impact of human-induced environmental alterations (although the terms “ecology” and “ecosystems” did not exist at that time) and extensive land use on human well-being [602]. Overexploitation (harvesting species from the wild at rates that exceed their reproductive capacity) and climate change have been identified as major drivers of biodiversity decline on Earth [603]. In one of the latest reports by the European Commission (EC), developed through collaboration between 50 experts from 25 EU Member States, a set of recommendations has been formulated to rethink the relationship between humans and nature, highlighting the role of human culture in achieving the Sustainable Development Goals (SDGs) [604]. Microalgae, in this regard, are being considered as a promising candidate that can directly or indirectly contribute to the SDGs [605], while also having historical roots in human culture. As carbon-hungry and nutrient-rich “sustainable biofactories”, microalgae offer potential solutions for global food security and mitigating environmental issues [606][607][606,607]. The historical roots of microalgae and its derivatives in human culture facilitate the reintroduction of algal biomass and algal bioactive functional ingredients, including AX, into global food and nutrition systems. Over the past few decades, studies on microalgae and their bioactive compounds, such as AX, have continuously revealed their role in promoting the circular economy and their positive effects on the health and well-being of the Earth and its flora and fauna. Although Haematococcus alga was discovered in the 18th century [222], its significance as a promising sustainable and abundant natural source of AX has garnered increasing attention in recent years. It is important to note that overexploitation of any flora and fauna, including algae and other carotenoids’ sources in nature (fruits and vegetables), may have an irreversible impact on the environment. In this case, well-designed and properly scaled commercial/artificial mass production of carotenoids seems to be more sustainable. In fact, sustainability potential includes the source from which AX and other carotenoids are obtained. Microalgae is considered a more sustainable source than other plant sources of carotenoids. For instance, the marigold flower is currently the predominant natural source of lutein. However, it has a lower growth rate than microalgae and requires arable land, and its harvest and extraction are only seasonal. Such limitations apply to other carotenoids from fruits and vegetables, such as zeaxanthin. There are some concerns about the sustainability of agricultural products as compared to algaculture, including the use of water, land, pesticides, and fertilizers. Microalgal cultivation has added environmental benefits over plants with higher carbon sequestration, a reduced water footprint, and no pesticide use. Both lutein and AX from microalgae can be considered sustainable active compounds, with even potentially complementary health benefits, especially for vision and eyes [608]. Currently, there is no commercial production of lutein from microalgae [609][610][609,610]. Moreover, although this review is focused on AX, it is noteworthy that this phytonutrient is only part of the algal meal. The whole microalgae biomass is consumable by humans and contains several high-value nutrients and bioactive molecules with health-promoting properties, including protein, essential fatty acids, antioxidant compounds, etc. For this reason, there is normally no or negligible amount of waste or residue produced from microalgae harvest, unlike other carotenoids extracted from agricultural products. |