Grant: Discovery Grants Program - Individual

Microorganisms have evolved an astoundingly versatile armamentarium of enzymes to degrade the vast array of organic compounds that occur in the environment. These enzymes constitute an essential link in the global carbon cycle, and as such are critical to maintaining the health of the biosphere. In addition to their fundamental importance, microbial catabolic enzymes represent an enormous, barely tapped source of biocatalysts for green chemistry and bioremediation. Understanding the huge natural diversity of microbial enzymes, and engineering them, facilitates the development of biocatalysts for more efficient, environmentally friendly industrial processes. My research program aims to investigate the structure and function of microbial enzymes involved in the degradation of natural and man-made compounds. NSERC-funded research has focused on enzymes that degrade biphenyl and PCBs (polychlorinated biphenyls), but has led to discoveries that impact health research (e.g., cholesterol degradation in tuberculosis) and the degradation of other compounds (e.g., explosives). Over the next five years, I propose to study three enzymes involved in degrading different pollutants: BphK dehalogenates PCB metabolites; acetonitrile hydratase degrades nitriles; and propane monooxygenase co-metabolizes N-nitrosodimethylamine, a groundwater contaminant and carcinogen. Each enzyme represents an important class of enzymes. Despite their importance, critical aspects of how these enzymes function remain unknown. The proposed research seeks to understand how the enzymes work (i.e., their catalytic mechanisms and roles of active site residues) and why they degrade some compounds but not others (i.e., the structural determinants of specificity). The results will provide fundamental insights into the molecular mechanism of important biological processes and facilitate their biotechnological exploitation. The research objectives will be achieved using a cutting-edge, interdisciplinary approach, including tools and methodologies unique to the Eltis lab. The proposed program provides students and postdoctoral researchers with a wide range of skills, thereby preparing them for careers in academia and industry.