Chemical probes reveal the timing of early chlorination in vancomycin biosynthesis

Glycopeptides such as vancomycin are antibiotics of last resort whose biosynthetic pathways still hold undefined details. Chemical probes were used to capture biosynthetic intermediates generated in the nonribosomal peptide formation of vancomycinin vivo. The putative intercepted intermediates were characterisedviaHR-LC-MS². These species provided insights into the timing of the first chlorination of the peptide backbone by the halogenase VhaA: this holds significant interest for enzyme engineering towards the making of novel glycopeptides.