Glyceryl‐S‐Acyl Carrier Protein as an Intermediate in the Biosynthesis of Tetronate Antibiotics

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Abstract
The biosynthetic pathway to the unusual tetronate ring of certain polyketide natural products, including the antibiotics abyssomicin and tetronomycin (TMN) and the antitumour compound chlorothricin (CHL), is presently unknown. The gene clusters governing chlorothricin and tetronomycin biosynthesis both contain a gene encoding an atypical member of the FkbH family of enzymes, which has previously been shown to synthesise glyceryl‐S‐acyl carrier protein (ACP) as the first step in production of unusual extender units for modular polyketide biosynthesis. We show here that purified recombinant FkbH‐like protein, Tmn16, from the TMN gene cluster catalyses the efficient transfer of a glyceryl moiety from D‐1,3‐bisphosphoglycerate (1,3‐BPG) to either of the dedicated ACPs, Tmn7a and ChlD2, to form glyceryl‐S‐ACP, which directly implicates this compound as an intermediate in tetronate biosynthesis as well. Neither Tmn16 nor Tmn7a produced glyceryl‐S‐ACP when incubated, respectively, with analogous ACP and FkbH‐like proteins from a known extender‐unit pathway; this indicates a highly selective channelling of glycolytic metabolites into tetronate biosynthesis.

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