ABSTRACT: Natural products have proven to be a reliable source of biomedically relevant compounds. Understanding the enzymatic mechanisms of natural product biosynthesis is critical for studies aimed at engineering or tailoring the structures of these useful molecules, which often remain refractory to total chemical synthesis. My lab focuses on elucidating the biosynthetic mechanisms of ribosomally-synthesized and posttranslationally modified peptides (RiPPs) – an interesting class of natural products where the genetically encoded precursor peptides are typically modified in multistep maturation processes by enzymes with relaxed substrate specificity. More specifically, our current work is focused on the class II lanthipeptide synthetases, enzymes that install sets of thioether rings into their precursor peptide substrates. Relying heavily on a suite of emerging biomolecular mass spectrometry-based techniques, our lab is investigating the chemical and kinetic mechanisms of lanthipeptide synthetases, and we are defining the underappreciated role of conformational changes and biophysical interactions in guiding the multistep lanthipeptide maturation process. This information is expected to be useful for the rational manipulation of functionally heterogeneous lanthipeptide synthetases and other RiPP biosynthetic enzymes.
BIO: Christopher J. Thibodeaux is a native of Louisiana, where he graduated valedictorian with bachelor's degrees in Biochemistry, Botany, and Chemistry from Louisiana State University. He then entered graduate school in the lab of Hung-wen Liu at the University of Texas, Austin, where his Ph.D. focused on elucidating the chemical and kinetic mechanisms of enzyme catalysis. Following graduation, he had postdoctoral stints in the labs of Taekjip Ha and Wilfred van der Donk at the University of Illinois, Urbana-Champaign, where he studied biomolecular single molecule fluorescence spectroscopy and peptide natural product biosynthesis, respectively. In 2016, he began his independent career in the Chemistry Department at McGill University, where he is currently an assistant professor.