Genome Mining of Myxopeptins Reveals a Class of Lanthipeptide-Derived Linear Dehydroamino Acid-Containing Peptides from Myxococcus sp. MCy9171

ACS Chem Biol. 2023 Oct 20;18(10):2163-2169. doi: 10.1021/acschembio.3c00265. Epub 2023 Sep 13.

Abstract

Myxobacteria exhibit a substantial capacity to produce bioactive natural products. The biosynthetic potential of ribosomally synthesized and post-translationally modified peptides (RiPPs) from myxobacteria remains largely underexplored. In our study, we identified a novel lanthipeptide-like biosynthetic pathway, mcy from Myxococcus sp. MCy9171, which was reconstituted in E. coli and in vitro proteolysis. Structural elucidation demonstrated that a series of dehydroamino acids were installed by an orphan McyB dehydratase onto the five McyA core peptides, named myxopeptins. Interestingly, compared with the canonical biosynthetic machinery of class I lanthipeptides, neither Cys residues existed in the diverse core regions, nor any LanC cyclase homologue was encoded in the mcy pathway. Thus, we propose myxopeptins as members of a new subclass of RiPPs, named lanthipeptide-derived linear dehydroamino acid-containing peptides (LDPs), which contain dehydrated amino acids as the class-defining post-translational modifications. Furthermore, sequence similarity network (SSN) analysis revealed the wide distribution of the biosynthetic potential of LDPs in various microbial phyla, implying a co-evolutionary scenario between the precursor peptide and class I lanthipeptide biosynthetic enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins* / genetics
  • Escherichia coli / metabolism
  • Hydro-Lyases* / genetics
  • Myxococcus* / metabolism
  • Peptides / chemistry
  • Protein Processing, Post-Translational

Substances

  • Peptides
  • McyB dehydratase, Myxococcus
  • Hydro-Lyases
  • Bacterial Proteins