The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties

Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19168-19177. doi: 10.1073/pnas.2004045117. Epub 2020 Jul 27.


The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues.

Keywords: RiPPs; Ruminococcin C; antibiotic; gut microbiome; sactipeptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Infections / drug therapy
  • Bacterial Infections / microbiology
  • Clostridiales / chemistry*
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / microbiology
  • Peptides / chemistry*
  • Peptides / isolation & purification
  • Peptides / pharmacology*


  • Anti-Bacterial Agents
  • Peptides

Supplementary concepts

  • Ruminococcus gnavus