Figure 1.

(A) The 6-deoxyerythronolide B synthase (DEBS), a prototypical assembly-line PKS, synthesizes 6-deoxyerythronolide B, the precursor of erythromycin A. (B–E) Reactions catalyzed by module 2 (M2) of DEBS. (B,C) Transacylation of the electrophilic and nucleophilic substrates of M2 from the ACP of module 1 (M1) and (2S)-methylmalonyl-CoA, respectively. (D,E) Polyketide chain elongation and ketoreduction. KS, ketosynthase; AT, acyltransferase; ACP, acyl carrier protein; KR, ketoreductase; KR⁰, redox-inactive KR with epimerase activity; DH, dehydratase; ER, enoylreductase; TE, thioesterase.