S144: RiPPs: Ribosomally Synthesized and Posttranslationally Modified Peptide Natural Products

Research in the 20^th century identified several major groups of natural products that were classified by common biosynthetic pathways such as terpenoids, polyketides, and non-ribosomal peptides. More recently, the genome sequencing efforts of the first decade of the 21^st century have revealed that another major class is formed by ribosomally synthesized and post-translationally modified peptides. These molecules are produced in all three domains of life, their biosynthetic genes are ubiquitous in the currently sequenced genomes, and their structural diversity is vast. Lantibiotics are examples of this growing class and many members are highly effective peptide-derived antimicrobial agents that display nanomolar minimal inhibitory concentrations (MICs) against pathogenic bacteria. These peptides are post-translationally modified to install multiple thioether crosslinks. During their biosynthesis, a single enzyme typically breaks 8-16 chemical bonds and forms 6-10 new bonds with high control over regio- and chemoselectivity.  This presentation will focus on the factors that control ring topology and stereoselectivity.