Radical SAM Enzymes and Ribosomally-Synthesized and Post-translationally Modified Peptides: A Growing Importance in the Microbiomes

To face the current antibiotic resistance crisis, novel strategies are urgently required. Indeed, in the last 30 years, despite considerable efforts involving notably high-throughput screening and combinatorial libraries, only few antibiotics have been launched to the market. Natural products have markedly contributed to the discovery of novel antibiotics, chemistry and drug leads, with more than half anti-infective and anticancer drugs approved by the FDA being of natural origin or inspired by natural products. Among them, thanks to their modular structure and simple biosynthetic logic, ribosomally synthesized and posttranslationally modified peptides (RiPPs) are promising scaffolds. In addition, recent studies have highlighted the pivotal role of RiPPs in the human microbiota which remains an untapped source of natural products. In this review, we report on recent developments in radical SAM enzymology and how these unique biocatalysts have been shown to install complex and sometimes unprecedented posttranslational modifications in RiPPs with a special focus on microbiome derived enzymes.

Automated summary

In order to address the antibiotic resistance crisis, novel strategies are urgently needed. Natural products have played a significant role in the discovery of new antibiotics, with ribosomally synthesized and posttranslationally modified peptides (RiPPs) being considered promising drug scaffolds. Recent studies have highlighted the important role of RiPPs in the human microbiota.