RaS-RiPPs in Streptococci and the Human Microbiome

Area of Science:

• Biochemistry
• Microbiology
• Natural Products Chemistry

Background:

• Radical S-adenosylmethionine (RaS) enzymes are a highly abundant and versatile enzyme superfamily.
• Their unique chemistry involves reductive cleavage of S-adenosylmethionine to initiate radical transformations.
• RaS enzymes play a crucial role in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), forming a class known as RaS-RiPPs.

Purpose of the Study:

• To review the discovery and characterization of RaS-RiPPs within the human microbiome.
• To highlight the role of RaS enzymes in generating complex natural products from peptide substrates.
• To emphasize the prevalence and significance of RaS-RiPPs in microbial communities, especially in the human microbiome.

Main Methods:

• Literature review focusing on RaS enzyme mechanisms and RiPP biosynthesis.
• Analysis of RaS-RiPPs found in human and mammalian microbiomes, with a specific focus on streptococcal bacteria.
• Discussion of the chemical modifications mediated by RaS enzymes on peptide substrates.

Main Results:

• RaS enzymes are involved in the biosynthesis of a diverse range of complex natural products (RaS-RiPPs).
• These metabolites are prevalent in the human microbiome, offering advantages for microbial survival in competitive environments.
• Streptococcal bacteria are a significant source of RaS-RiPPs in the human microbiome.

Conclusions:

• RaS enzymes enable the production of complex RiPPs with minimal energetic and genomic cost, favoring their presence in microbial communities.
• The study underscores the importance of RaS-RiPPs in the human microbiome and their potential as a source of novel natural products.
• A vast majority of RaS-RiPPs remain undiscovered, presenting exciting opportunities for future research at the interface of enzymology, chemical ecology, and microbiome studies.