Supramolecular Templating in Kirromycin Biosynthesis: The Acyltransferase KirCII Loads Ethylmalonyl-CoA Extender onto a Specific ACP of the trans-AT PKS

SummaryIn the biosynthesis of complex polyketides, acyltransferase domains (ATs) are key determinants of structural diversity. Their specificity and position in polyketide synthases (PKSs) usually controls the location and structure of building blocks in polyketides. Many bioactive polyketides, however, are generated by trans-AT PKSs lacking internal AT domains. They were previously believed to use mainly malonyl-specific free-standing ATs. Here, we report a mechanism of structural diversification, in which the trans-AT KirCII regiospecifically incorporates the unusual extender unit ethylmalonyl-CoA in kirromycin polyketide biosynthesis.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (187 K)Download as PowerPoint slideHighlights► The acyl transferase KirCII is essential for kirromycin biosynthesis ► KirCII is loading ethylmalonyl-CoA to a specific ACP of the kirromycin PKS ► Supramolecular templating - a new alternative for generating polyketide diversity