Characterization of the Calicheamicin Orsellinate C2‐ O ‐Methyltransferase CalO6

Although bacterial iterative type I polyketide synthases are now known to participate in the biosynthesis of a small set of diverse natural products, the subsequent downstream modification of the resulting polyketide products is poorly understood. We report the functional characterization of the putative orsellinic acid C2‐ O ‐methyltransferase, which is involved in calicheamicin biosynthesis. This study suggests that C2‐O‐methylation precedes C3‐hydroxylation/methylation and C5‐iodination and requires a coenzyme A‐ or acyl carrier protein‐bound substrate.