Characterization of Heronamide Biosynthesis Reveals a Tailoring Hydroxylase and Indicates Migrated Double Bonds

Heronamides belong to a growing family of β‐amino acid polyketide macrolactams (βPMs) with an unsaturated side chain. The biosynthetic gene cluster for heronamide F was identified from the deep‐sea‐derived Streptomyces sp. SCSIO 03032. The involvement of the gene cluster in heronamide biosynthesis was confirmed by the functional characterization of the P450 enzyme HerO as an 8‐hydroxylase for tailoring heronamide biosynthesis. The presence of migrated double bonds in the conjugated diene‐containing side chain of heronamides was confirmed by feeding experiments with labeled small carboxylic acid molecules. This study is the first demonstration of migrated double bonds in βPMs with an unsaturated side chain. Migrated double bonds: A P450 enzyme HerO was functionally characterized as the C‐8 hydroxylase tailoring heronamide biosynthesis. Migrated double bonds in the biosynthesis of the unsaturated side chain were indicated by feeding with labeled small carboxylic acid molecules.