Brandon Greene

Title: "The radical lives of anaerobes and how to fight them"

Abstract: Pathogenic bacteria that infect the gastrointestinal and respiratory tract form biofilms that are largely anaerobic, modulating their metabolic lifestyle and virulence. Many of these microbes utilize mixed fermentation via the enzyme pyruvate formate lyase (PFL), which catalyzes the production of acetyl-CoA and formate from pyruvate via a radical mechanism, providing bioenergetic competitiveness and critical metabolites for anabolic biosynthesis. In this talk, I will describe our lab’s work developing a molecular-level picture of catalysis and radical transfer regulation in PFL. I will also summarize our findings that nitric oxide (NO), a principal agent of the innate immune response, is an irreversible inhibitor of PFL and glycyl radical enzymes as a class, as well as their radical S-adenosyl-L-methionine-dependent activases. In vivo, NO profoundly alters metabolism in anaerobically growing E. coli, providing a potential roadmap for spatio- and temporally-resolved narrow-spectrum antibiotic development for the treatment of gastrointestinal and pulmonary disease that complement the innate immune response.

Biography: Brandon was born in Spokane, WA and completed his B.S. in chemistry at Washington State University. During his PhD studies at Emory University, under the direction of R. Brian Dyer, he developed chemical potential jump transient kinetic approaches to determine the catalytic mechanism of hydrogenases. As a postdoc with Daniel G. Nocera and JoAnne Stubbe he continued his studies on proton-coupled electron transfer in ribonucleotide reductase. He started his independent lab at UCSB in 2019, which focuses on non-equilibrium redox biology.