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Fig. 1 | Biological Research

Fig. 1

From: The SREBP (Sterol Regulatory Element-Binding Protein) pathway: a regulatory bridge between carotenogenesis and sterol biosynthesis in the carotenogenic yeast Xanthophyllomyces dendrorhous

Fig. 1

Biosynthesis of astaxanthin and ergosterol in X. dendrorhous. The production of carotenoids and sterols requires isopentenyl pyrophosphate (IPP) from the mevalonate pathway [9]. Carotenoid biosynthesis begins with the production of geranylgeranyl pyrophosphate (GGPP) from farnesyl pyrophosphate (FPP) and IPP by GGPP synthase encoded by crtE [66, 68]. Then, the bi-functional enzyme phytoene-β-carotene synthase encoded by crtYB condenses two GGPP molecules producing phytoene [69]. Subsequently, phytoene undergoes four desaturation reactions carried out by the phytoene desaturase enzyme encoded by crtI, producing lycopene [70]. The cyclization of both ends of lycopene by the lycopene cyclase activity of the phytoene-β-carotene synthase produces β-carotene [69], which is then transformed into astaxanthin via intermediate xanthophylls. To date, X. dendrorhous is the only known organism that produces astaxanthin from β-carotene through a cytochrome P450 system [71], which is composed of the cytochrome P450 enzyme astaxanthin synthase (CrtS, encoded by crtS) [72, 73] and a cytochrome P450 reductase (CPR) (named CrtR in X. dendrorhous, encoded by crtR) [64]. CrtS catalyzes the hydroxylation and ketolation of carbons at positions 3 and 4, respectively, of each end ring of β-carotene to finally produce astaxanthin [72], while CrtR assists CrtS in these reactions [64]. In ergosterol biosynthesis, two cytochrome P450 enzymes are involved, which are encoded by CYP51 (lanosterol 14α-demethylase) [74] and CYP61 (C-22 sterol desaturase) [49]. Arrows: catalytic steps with the corresponding enzyme encoding gene. Genes in red: Direct Sre1 targets identified by ChIP-exo [17]. CrtR was included as a redox partner of the cytochrome P450 monooxygenases Cyp51, Cyp61 and CrtS, and squalene epoxidase (ERG1). 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA), mevalonate (MVA), dimethylallyl-pyrophosphate (DMAPP). Other genes: ERG10 (acetyl-CoA C-acetyltransferase), HMGS (HMG-CoA synthase), HMGR (HMG-CoA reductase), MVK (mevalonate kinase), PMK (phosphomevalonate kinase), MVD (mevalonate diphosphate decarboxylase), idi (IPP isomerase), FPS (FPP synthase). ERG represent to enzyme-encoding genes involved in ergosterol biosynthesis identified in Saccharomyces cerevisiae. Figure adapted from [17]

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