Ribosomal Synthesis of Natural-Product-Like Bicyclic Peptides in Escherichia coli.

ABSTRACT: Methods to access natural-product-like macrocyclic peptides can disclose new opportunities for the exploration of this important structural class for chemical biology and drug discovery applications. Here, the scope and mechanism of a novel strategy for directing the biosynthesis of thioether-bridged bicyclic peptides in bacterial cells was investigated. This method entails split intein-catalyzed head-to-tail cyclization of a ribosomally produced precursor peptide, combined with inter-side-chain crosslinking through a genetically encoded cysteine-reactive amino acid. This strategy could be successfully applied to achieve formation of structurally diverse bicyclic peptides with high efficiency and selectivity in Escherichia coli. Insights into the sequence of reactions underlying the peptid

SUBMITTER: Bionda N 

PROVIDER: S-EPMC4573908 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature