Divisional Seminar

Department of Chemistry

Title: "Elucidation of the chemical and biological roles of five carbon metabolism" 

Five-carbon metabolism derives from the central hub of the isoprenoid pathway, which is necessary for an array of critical bioactivities, including cell membrane integrity (e.g., cholesterol), glycoprotein synthesis (e.g., the dolichols), steroid hormone signaling (e.g., androgens, estrogens, and cortisol), and mitochondrial health (e.g., coenzyme Q). Human isoprenoids derive from the mevalonic acid (MVA) pathway, whereas many other organisms utilize the methyl erythritol phosphate (MEP) pathway. The MVA and MEP pathways both converge on the same two isomeric C5 metabolites, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). Therefore, IPP and DMAPP are the central five-carbon precursors for all isoprenoids in all organisms. Despite their importance, there are relatively few chemical and biological tools to directly study IPP and DMAPP and little is understood about their independent biological activity, and metabolic fate beyond incorporation into longer chain isoprenoids. Similarly, chemical tools developed for studying prenylation via the long-chain isoprenoids farnesyl pyrophosphate (C15) and geranylgeranyl pyrophosphate (C20) are well-established, but tools and approaches for interrogating C5 prenylation are lacking. My seminar will focus on our efforts to bridge these scientific gaps through the development of cell-permeant analogs of IPP and DMAPP. Specifically, I will discuss how these chemical tools used in combination with high-resolution mass spectrometry reveals novel biological functions of C5 metabolism in human cancer cell lines and the model Gram positive bacterium Bacillus subtilis.

Josh grew up in Big Flats, New York, and attended SUNY Cortland for his B.S. in Chemistry working on the synthesis of photocleavable peptide conjugates under Prof. Frank Rossi. He then moved 30 minutes away to get his Ph.D. under Frank Schroeder in the Department of Chemistry and Chemical Biology at Cornell University. His graduate research focused on the discovery and characterization of novel biosynthetic pathways and metabolites from filamentous fungi. After his Ph.D, Josh went across the country to do postdoctoral research in Prof. David Tirrell’s lab at Caltech in the Division of Chemistry and Chemical Engineering. His postdoctoral research was focused on the development of artificial protein force sensors in hydrogels. In August of 2020 Josh moved to Knoxville, TN and started his lab in the Department of Chemistry at the University of Tennessee, Knoxville.