FIG 1.

Modular biosynthesis of yersiniabactin (Ybt). A salicylate starter unit is activated by YbtE, via adenylation (A), prior to transfer to the first nonribosomal peptide synthetase module of HMWP2, which subsequently introduces and cyclizes two cysteine groups. Upon transfer to HMWP1, a polyketide synthase model introduces a malonyl-CoA unit whose carbonyl group is reduced and methylated in NADPH- and SAM-dependent steps via the activity of dedicated ketoreductase (KR) and methyltransferase (MT) domains. The second module of HMWP1 introduces and cyclizes a third cysteine unit. A terminal thioesterase (TE) domain releases the mixed nonribosomal peptide-polyketide chain from HMWP1 prior to a final reduction step by YbtU. ArCP, aryl carrier protein; Cy, cyclization domain; PCP, peptidyl carrier protein; KS, ketosynthase; AT, acyltransferase; Red, reductase.