Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a diverse class of natural products, typically encoded within the genome as part of biosynthetic gene clusters. Recently, several multinuclear non-heme iron dependent oxidative enzymes (MNIOs, formerly known as DUF692 enzymes) found within bacterial RiPP gene clusters have been reported to catalyze unusual rearrangements on peptide substrates. My research in the van der Donk group aims to explore the mechanism of ChrH, an MNIO from the Chryseobacterium genus that performs a remarkable rearrangement on a peptide precursor to form a hydantoin heterocycle, a macrocycle, two thioaminals, and a thiomethyl group. Since hydantoins are privileged scaffolds that are found in several antimicrobials and anticonvulsants, understanding the biosynthesis and function of this natural product could lay the foundation towards engineering novel bioactive compounds.
Advisor: Wilfred van der Donk