Mechanism

The van der Donk lab is interested in the mechanistic studies of RiPP (ribosomally synthesized and post-translationally modified peptide) and phosphonate biosynthesis. We are particularly interested in probing the intricate mechanisms behind biosynthetic enzymes and how basic chemical principles govern reactivity, site selectivity, and steroselectivity. By employing a combination of protein engineering, structural biology, non-proteinogenic amino acid incorporation, and kinetic spectroscopic techniques, we have shed light on the mechanisms of several enzymes involved in RiPP and phosphonate biosynthesis. Elucidating key mechanistic insights into the complex post-translational modifications that occur during natural product maturation serves as a foundation for developing new strategies for RiPP synthesis and bioengineering.