The Biosynthesis of Vancomycin‐Type Glycopeptide Antibiotics—A Model for Oxidative Side‐Chain Cross‐Linking by Oxygenases Coupled to the Action of Peptide Synthetases

Model mutants. The biosynthesis of glycopeptide antibiotics must be understood before it can be reprogrammed to generate altered antibiotics. Based on a detailed HPLC-ESI-MS analysis of linear and cyclic peptide intermediates of balhimycin biosynthesis mutants, a new model for glycopeptide assembly is suggested (see figure). We propose that the three central oxidative cyclizations by P450-dependant monooxygenases occur during peptide assembly before cleavage from the nonribosomal peptide synthetase complex.