Wilfred Van der Donk
Professor of Chemistry, University of Illinois at Urbana-Champaign
Combinatorial Methods Towards Genetically Encoded Cyclic Peptides
The genome sequencing efforts of the first decade of the 21st century have revealed that ribosomally synthesized and post-translationally modified peptides (RiPPs) constitute a very large class of cyclic peptide natural products. 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. Lanthionine-containing peptides (lanthipeptides) 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 (lantibiotics). 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 region and chemoselectivity. This presentation will discuss use of the lanthipeptide biosynthetic machinery for the generation of non-natural cyclic peptide libraries.