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- Title
Discovery and biosynthesis of tricyclic copper-binding ribosomal peptides containing histidine-to-butyrine crosslinks.
- Authors
Li, Yuqing; Ma, Yeying; Xia, Yinzheng; Zhang, Tao; Sun, Shuaishuai; Gao, Jiangtao; Yao, Hongwei; Wang, Huan
- 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 the first copper-binding lanthipeptide. A subgroup of lanthipeptide synthetases, named LanKCHbt, were identified to catalyze the formation of both the labionin and the histidinobutyrine crosslinks in precursor peptides and produce noursin-like compounds. The discovery of the histidinobutyrine-containing lanthipeptides expands the scope of post-translational modifications, structural diversity and bioactivity of ribosomally synthesized and post-translational modified peptides. Cyclic peptides are important bioactive compounds and drugs, synthesised by enzymatic side-chain macrocyclization of ribosomal peptides, which rarely involves histidine residues. Here, the authors report the discovery and biosynthesis of tricyclic lanthipeptide noursin, constrained by a tri amino acid labionin crosslink and histidine-to-butyrine crosslink, which is important for copper binding of noursin.
- Subjects
PEPTIDES; CYCLIC peptides; BIOACTIVE compounds; BIOSYNTHESIS; NEUROPEPTIDES; POST-translational modification; AMINO acids; CROSSLINKED polymers; MACROCYCLIC compounds
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-38517-2