With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Pinghua Liu from Boston University to characterize the enzymes that catalyze the formation of C-S bonds in the ergothioneine biosynthesis. Although sulfur-containing molecules, both small molecules and macromolecules, play many important roles in biological systems and sulfur represents one percent of the entire cell dry weight, to date, details of the biosynthesis of the vast majority of sulfur-containing molecules are still missing. Hence, C-S bond formation reactions are at the frontier of natural product chemistry and mechanistic enzymology. New insight into the details these reactions may have downstream applications to industrial processes for the synthesis of sulfur-containing molecules. The interdisciplinary nature of the work renders it an excellent platform to train students on the path to STEM careers. The central educational objective is that students learn how to apply knowledge gained in basic research to solve real world problems.
This award focuses on the C-S bond formation reactions catalyzed in biological systems by enzymes,specifically on the elucidation of the mechanism of C-S bond formation in the biosynthesis of ergothioneine. These reactions are unique because they involve an unactivated sp2 C-H bond and because nature has evolved two different ways to activate this bond to produce a C-S bond, one aerobic and another anaerobic. The Liu team will use the tools of x-ray structure determination, computational protein design, unnatural amino acid mutagenesis, and kinetic measurements to gain insight into the mechanism of these enzyme-mediated transformations. For the aerobic pathway, Dr. Liu systematically evaluates structure-function relationships for key non-heme iron enzymes that catalyze C-S bond formation reactions and applies the new knowledge to differentiate among a few mechanistic models for the reaction. For the anaerobic pathway, the research focuses on the study of the source of sulfur for the C-S bond formation reactions and the elucidation of the biological role of these anaerobic reactions.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
