Novel chemical probes to probe the metabolism and mode of action of fungicides

Ensuring a sufficient and sustainable food supply to meet the needs of the currently increasing global population has become one of the most important scientific and technological challenges facing society. Systemic fungicides constitute a critical tool for maintaining agricultural productivity and hence a crucial part of the future road map for sustainable crop production. However, resistance presents a constant challenge to the effectiveness of fungicides and one significant source of resistance is metabolic P450 enzyme adaption within fungi resulting in rapid oxidative clearance of fungicides.

This project will develop and apply novel chemical methods for the identification of the specific enzymes responsible for detoxification of a given fungicide. We will probe the site and mode of chemical reaction of these enzymes to aid our understanding of fungal detoxification pathways to allow for the design of more effective fungicides in the future. The plan is to immobilise fungicidal compounds onto various support matrices via linkers/spacers co-functionalised with cross-linking ‘warhead’ functionality and employ these as pull-down probes. Overall, the project will involve the integration of synthetic chemistry, chemical biology and biochemistry to create tailored protocols for the rapid mapping of fungicide-protein interactomes.