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Fig. 1 | Microbial Cell Factories

Fig. 1

From: Refactoring the architecture of a polyketide gene cluster enhances docosahexaenoic acid production in Yarrowia lipolytica through improved expression and genetic stability

Fig. 1

Genetic and metabolic design to produce docosahexaenoic acid (DHA) in Yarrowia lipolytica through heterologous expression of a myxobacterial PKS-like PUFA synthase gene cluster. The PUFA cluster from Aetherobacter fasciculatus (SBSr002) comprised the three genes pfa123, encoding the multidomain subunits of the PUFA synthase, as well as ppt, encoding 4'-phosphopantetheinyl transferase (PPTase) (A). The biosynthesis of DHA by PUFA synthase starts with acetyl-CoA, which binds to the ketosynthase domain and is then successively elongated with activated malonyl-CoA units bound to an acyl carrier protein (ACP) (B). Within each cycle, decarboxylative Claisen condensations form β-keto ester intermediates, which are then reduced to the corresponding alcohols. Then, dehydration inserts an α, β-trans double bond, which is either reduced or isomerized into the cis form. After ten cycles, the formed DHA fatty acyl chain is transferred to the 2-position of 1-acylglycerol-3-phosphate by 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT)

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