FIGURE 14.

CrpD inserts ester bonds during elongation and termination steps in cryptophycin biosynthesis. (a) The C domain in CrpD Module 2 catalyzes ester bond formation between the growing polyketide‐peptide chain and an α‐hydroxy acid. The TE domain catalyzes cyclization using the OH group in the polyketide portion as nucleophile, releasing a cryptophycin precursor. The cycle proceeds in off‐assembly line reactions. (b) The A‐KR‐PCP module in CrpD activates and reduces an α‐ketoacid to generate an α‐hydroxy acyl thioester. Figure based on Magarvey et al. ³⁸