Fig. 1

Vitamin A biosynthesis. a Biosynthesis of retinal and its conversion to other retinoids. BCDO, β-carotene 15,15ʹ-dioxygenase; BCMO, β-carotene 15,15′-monooxygenase; ACO, apo-carotenoid 15,15′-oxygenase; ALDH, aldehyde dehydrogenase; SDR, short-chain dehydrogenase/reductase; AKR, aldo-keto reductase; ADH, alcohol dehydrogenase. b Vitamin A biosynthetic pathway in S. cerevisiae. The biosynthetic pathway starts from the endogenous mevalonic acid (MVA) pathway, extended by a β-carotene synthetic pathway module consisting of CrtE03M, CrtYB and CrtI from Xanthophyllomyces dendrorhous and the vitamin A formation module containing the Halobacterium sp. β-carotene dioxygenase gene BLH and the retinal reductase genes (ybbO from E. coli and ENV9 from S. cerevisiae). The major competing branches for the key precursor farnesyl pyrophosphate (FPP) include the ergosterol synthetic pathway and the phosphatase-catalyzed formation of farnesol. Diacylglycerol pyrophosphate phosphatase gene DPP1 and lipid phosphate phosphatase gene LPP1 were knocked out and used as integration sites. The exogenous enzymes introduced are shown in green, the endogenous enzymes are depicted in orange and those deleted are depicted in gray. HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA; FPP, farnesyl pyrophosphate; GGPP, geranylgeranyl diphosphate; tHmg1, truncated 3-hydroxy-3-methyl-glutaryl reductase; CrtE, geranylgeranyl diphosphate synthase; CrtI, phytoene desaturase; CrtYB, phytoene synthase/ lycopene cyclase; Blh, bacterirhodopsin-related-protein-like homolog protein (later identified as β-carotene dioxygenase); ybbO, aldehyde reductase; tPos5, truncated NADH kinase