Control Mechanism for Carbon‐Chain Length in Polyunsaturated Fatty‐Acid Synthases

Abstract

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The lipid metabolism in thraustochytrids

“…The CLF domain shows homology with KS but lacks active site residues and is thus assumed to be inactive, a situation similar to the one found in type II PKS [102]. This domain has been functionally characterized in association with its KS neighbour domain [103] and plays an important role in the carbon chain elongation, especially for the elongation from C20 to C22 (EPA to DHA). In thraustochytrids it also controls the final yield of PUFA production [104].…”

“…The first DH domain in subunit A is similar to the one found in PKS and only catalyses the dehydration reaction. The DH domains associated with subunit C present high homology with FabA [103], one of the two acyl-ACP dehydratases involved in the biosynthesis of FAs in E. coli. Besides catalysing the dehydration reaction, FabA also isomerizes trans-2-decenoyl-ACP into cis-3-decenoyl-ACP, an essential step to produce PUFAs in these bacteria.…”

“…The specificity of the various PUFA synthases relies probably more on specific or structural details than just its global organization. From this point of view, it was recently shown that the type of PUFA produced in bacteria was determined by the subunit C of these organisms [103]. Indeed, when the KS-CLF domains of an EPA synthase is replaced by the KS-CLF domains of a DHA synthase, the resulting chimeric EPA synthase is able to produce DHA.…”

“…Putative scheme illustrating the reactions catalyzed by the PUFA synthase. This scheme relies on previous reports describing the functions of the different domains [103][104][105]. Compared with the reactions catalyzed by the classical FAS I system, the main differences would be at the level of the DH/I and ER steps, allowing or not the formation of a cis-double bond [92,105].…”

“…Compared with the reactions catalyzed by the classical FAS I system, the main differences would be at the level of the DH/I and ER steps, allowing or not the formation of a cis-double bond [92,105]. Also, the potential role of the CLF domain to terminate the elongation process [102][103][104], and how the FA is released from the synthesizing complex, remain open questions. On the higher part of the drawing, acetyl-CoA and malonyl-CoA are condensed to form a starter-ACP unit, then at each round two carbons from a malonyl-CoA are condensed to the growing chain, thanks to the MAT and KS domains.…”