RaS-RiPPs in Streptococci and the Human Microbiome

Kenzie A. Clark, Leah B. Bushin, Mohammad R. Seyedsayamdost

Research output: Contribution to journalReview articlepeer-review

Abstract

Radical S-adenosylmethionine (RaS) enzymes have quickly advanced to one of the most abundant and versatile enzyme superfamilies known. Their chemistry is predicated upon reductive homolytic cleavage of a carbon-sulfur bond in cofactor S-adenosylmethionine forming an oxidizing carbon-based radical, which can initiate myriad radical transformations. An emerging role for RaS enzymes is their involvement in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a natural product family that has become known as RaS-RiPPs. These metabolites are especially prevalent in human and mammalian microbiomes because the complex chemistry of RaS enzymes gives rise to correspondingly complex natural products with minimal cellular energy and genomic fingerprint, a feature that is advantageous in microbes with small, host-adapted genomes in competitive environments. Herein, we review the discovery and characterization of RaS-RiPPs from the human microbiome with a focus on streptococcal bacteria. We discuss the varied chemical modifications that RaS enzymes introduce onto their peptide substrates and the diverse natural products that they give rise to. The majority of RaS-RiPPs remain to be discovered, providing an intriguing avenue for future investigations at the intersection of metalloenzymology, chemical ecology, and the human microbiome.

Original languageEnglish (US)
Pages (from-to)328-339
Number of pages12
JournalACS Bio and Med Chem Au
Volume2
Issue number4
DOIs
StatePublished - Aug 17 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Pharmaceutical Science

Keywords

  • mechanism
  • microbiome
  • natural products
  • radical SAM enzymes
  • RiPPs
  • sequence similarity network
  • streptococcus

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