Biochemical dissection of a fungal highly reducing polyketide synthase condensing region reveals basis for acyl group selection.

ABSTRACT: Fungal highly reducing polyketide synthases (hrPKSs) are remarkable multidomain enzymes that catalyse the biosynthesis of a diverse range of structurally complex compounds. During biosynthesis, the ketosynthase (KS) and acyltransferase (AT) domains of the condensing region are visited by the acyl carrier protein (ACP) domain during every cycle, catalysing chain priming and elongation reactions. Despite their significance, our comprehension of how these steps contribute to biosynthetic fidelity remains poorly understood. Using the SimG hrPKS from the cyclosporin pathway as a model system, we report the full in vitro reconstitution of each catalytic step carried out by a hrPKS condensing region. Application of intact protein mass spectrometry shows that the AT domain operates selectiv

SUBMITTER: Foran ME 

PROVIDER: S-EPMC12199272 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature