Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase.

Abstract

The N-sulfonated monocyclic β-lactam ring characteristic of the monobactams confers resistance to zinc metallo-β-lactamases and affords the most effective class to combat carbapenem-resistant enterobacteria (CRE). Here we report unprecedented non-ribosomal peptide synthetase activities where an assembled tripeptide is N-sulfonated in trans prior to direct synthesis of the β-lactam ring in a non-canonical, cysteine-containing thioesterase domain. This means of azetidinone synthesis is distinct from the three others known in nature.