Biosynthesis of Antituberculosis Antibiotic Capreomycin Involves a trans-Iterative Adenylation Domain within the Nonribosomal Peptide Synthetase Machinery

Capreomycin (CMN) is a nonribosomal peptide (NRP) antituberculosis antibiotic. CMN biosynthesis involves a non-canonical trans-iterative adenylation (A) domain. Here, we report that the A domain-less nonribosomal peptide synthetase (NRPS) module CmnI utilizes another module's A domain CmnA-A(1) to load the required amino acid onto its thiolation (T) domain. This study provides evidence of an unusual mode of NRP biosynthesis in bacteria, involving a trans-iterative A domain in the NRPS machinery.