Methyltransferase Domain‐Focused Genome Mining for Fungal Polyketide Synthases

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.