Bioinspired strategy for the ribosomal synthesis of thioether-bridged macrocyclic peptides in bacteria.

ABSTRACT: Inspired by the biosynthetic logic of lanthipeptide natural products, a new methodology was developed to direct the ribosomal synthesis of macrocyclic peptides constrained by an intramolecular thioether bond. As a first step, a robust and versatile strategy was implemented to enable the cyclization of ribosomally derived peptide sequences via a chemoselective reaction between a genetically encoded cysteine and a cysteine-reactive unnatural amino acid (O-(2-bromoethyl)-tyrosine). Combination of this approach with intein-catalyzed protein splicing furnished an efficient route to achieve the spontaneous, post-translational formation of structurally diverse macrocyclic peptides in bacterial cells. The present peptide cyclization strategy was also found to be amenable to integration with split

SUBMITTER: Bionda N 

PROVIDER: S-EPMC4168796 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature