Methyltransferase Domain‐Focused Genome Mining for Fungal Polyketide Synthases

Abstract A comparison of substrate‐binding site amino acid residues in the C‐methyltransferase (MT) domains of fungal nonreducing polyketide synthases (NR‐PKSs) suggests that these residues are correlated with the methylation modes used by the PKSs. A PKS, designated as AsbPKS, with substrate‐binding site residues distinct from those of other known PKSs is focused on. The characterization of AsbPKS revealed that it yields an isocoumarin derivative, anhydrosclerotinin B (1), the biosynthesis of which involves a previously unreported methylation pattern. This study demonstrates the utility of MT domain‐focused genome mining for the discovery of PKSs with new functions.