Biosynthesis of Antituberculosis Antibiotic Capreomycin Involves a <i>trans</i>-Iterative Adenylation Domain within the Nonribosomal Peptide Synthetase Machinery.

ABSTRACT: 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-A₁ 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.

SUBMITTER: Lai YT 

PROVIDER: S-EPMC12400406 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature