Grant: Discovery Grants Program - Individual

Microbes generate an astounding array of diverse chemistry, including an unusual class of molecules possessing a carbon-phosphorus (C-P) bond called phosphonates. Although some (e.g. the antibiotic fosfomycin) have been intensively studied and led to commercial success, phosphonates remain an overlooked class of natural molecules. Even more underexplored are naturally-occurring phosphonate modifications of cell surfaces. Although predicted to be widespread in Nature, startlingly few of these modifications have been characterized, and virtually nothing is known about their biological roles. Chemically, phosphonates are less oxidized and more resistant to hydrolytic cleavage than their phosphate cousins that dominate central metabolism in all organisms. For microbes, this implies possible roles in low oxygen environments or in evading host lysosomal defences. This research program is systematically identifying and characterizing phosphonate modifications and understanding how they are manufactured in the bacterial cell. In addition to revealing how cell surface phosphonates are made and what they are doing, we aim to harness these catalytic activities to develop sustainable technologies for manufacturing modified biomaterials. Specifically, using enzyme biocatalysts to modify polymeric materials does not require chlorinated organic solvents, extreme temperatures, or heavy metals required in traditional chemical synthetic routes. In addition to lower energy input and reduced toxic waste, the contaminant-free products meet high standards required for biomedical applications.