Ruminococcin C， a promising antibiotic produced by a human gut symbiont.

A major public health challenge today is the resurgence of microbial infections caused by multidrug-resistant strains. Consequently， novel antimicrobial molecules are actively sought for development. In this context， the human gut microbiome is an under-explored potential trove of valuable natural molecules， such as the ribosomally-synthesized and post-translationally modified peptides (RiPPs). The biological activity of the sactipeptide subclass of RiPPs remains under-characterized. Here， we characterize an antimicrobial sactipeptide， Ruminococcin C1， purified from the caecal contents of rats mono-associated with E1， a human symbiont. Its heterologous expression and post-translational maturation involving a specific sactisynthase establish a thioether network， which creates a double-hairpin folding. This original structure confers activity against pathogenic and multidrug-resistant strains but no toxicity towards eukaryotic cells. Therefore， the Ruminococcin C1 should be considered as a valuable candidate for drug development and its producer strain E1 as a relevant probiotic for gut health enhancement.