Title: Nonribosomal peptide synthetases (NRPSs) are true macromolecular machines, having modular assembly-line logic, a complex catalytic cycle, moving parts and many active sites. NRPS products include classics therapeutics (penicillin, cyclosporin, and modern billion-dollar antibiotics (daptomycin) and anti-cancer agents (dactinomycin). We have performed structural and functional analyses of components of the NRPS systems responsible for the syntheses of the antibiotic gramicidin, the siderophore bacillibactin and the anti-algae bacillamide. I will discuss results from these studies and the insight they provide into the superdomain and supermodular architecture, conformational changes and mechanisms of tailoring NRPSs use to synthesize their important bio-active products.
Bio: Martin Schmeing received his B.Sc. from McGill University (1998), before obtaining his M.Sc. and Ph.D. with Dr. Thomas Steitz at Yale University (2002, 2004). He then carried out postdoctoral research with Dr. V. Ramakrishnan at the Laboratory of Molecular Biology, Cambridge, UK (2005-2010). He was appointed Assistant Professor at the Department of Biochemistry, McGill University in 2010, and was promoted to Associate Professor in 2016. He holds a Canadian Research Chair in Macromolecular Machines and serves as the Director of the Centre for Structural Biology, and Associate Director for the Facility for Electron Microscopy Research. The main focus of his research is on elucidating the structures and functions of nonribosomal peptide synthetases (NRPSs). NRPSs are large microbial enzymes that synthesize their products through amide bond formation between building block monomers (most commonly amino acids). The chemical and biological properties of these compounds often make them useful to society as therapeutics (antibiotics, antivirals, anti-tumours, and immunosuppressants) and as natural green chemicals (emulsifiers, siderophores, and research tools). Two aspects of particular focus in Dr. Schmeing’s research are the catalytic event which links substrate building blocks, and the manner in which NRPS domains and modules work together in a complicated and productive catalytic cycle. His work has been recognized with honours including the Young Investigator Award from Canadian Society for Molecular Biosciences, Joe Doupe Award from the Canadian Society for Clinical Investigation, Bhagirath Singh Early Career Award from the Canadian Institutes of Health Research, and a Career Development Award from the Human Frontier Science Program Organization.