Discovery and biosynthesis of tricyclic copper-binding ribosomal peptides containing histidine-to-butyrine crosslinks.

ABSTRACT: Cyclic peptide natural products represent an important class of bioactive compounds and clinical drugs. Enzymatic side-chain macrocyclization of ribosomal peptides is a major strategy developed by nature to generate these chemotypes, as exemplified by the superfamily of ribosomally synthesized and post-translational modified peptides. Despite the diverse types of side-chain crosslinks in this superfamily, the participation of histidine residues is rare. Herein, we report the discovery and biosynthesis of bacteria-derived tricyclic lanthipeptide noursin, which is constrained by a tri amino acid labionin crosslink and an unprecedented histidine-to-butyrine crosslink, named histidinobutyrine. Noursin displays copper-binding ability that requires the histidinobutyrine crosslink and represents

SUBMITTER: Li Y 

PROVIDER: S-EPMC10206099 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature