Development of Natural Product-Inspired Ubiquinone Mimics as Next Generation Agrochemicals

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With the support of the Chemistry in Life Processes program in the Division of Chemistry, Professor William Wuest of Emory University is developing novel agrochemicals inspired by compounds produced in nature. Blight is a disease that kills large quantities of crops and is primarily caused by bacteria and fungi. The organisms that cause blight continually evolve to resist the treatments that farmers use causing these practices to fail. Therefore, chemists will need to continuously identify new methods to sustain current farming practices. Two compounds have been identified that target blight-causing organisms and chemical methods and biological tests will be used to validate the proposed hypotheses. These studies will provide an ideal training ground for undergraduate and graduate students to develop specialized skills in organic synthesis and will prepare them for careers in either academia or industry. The project also integrates two outreach programs focusing on graduate student career development. The first program will provide training in course design for graduate students while simultaneously teaching undergraduates about the process of joining a research lab in college. The second program specifically trains graduate students in innovation, entrepreneurship, and consulting through their involvement in the activities provided by the Emory Biotech Consulting Club.The research project seeks to characterize and develop natural products and derivatives thereof for their implementation as inhibitors of agriculturally relevant pathogens. Focus will be placed on compounds found within the rhizosphere as they have likely evolved to specifically inhibit plant pathogens. This proposal will use a variety of methods ranging from synthetic organic chemistry to microbiology to interrogate two specific families of natural products that likely mimic the natural cofactor ubiquinone. Specifically, this investigation is focused on the synthesis and evaluation of peniciaculin-inspired inhibitors of plant pathogens of 4-hydroxypyridinone natural products. With a better understanding of the key interactions of these natural products with their targets, further enabled through the collaboration with industry partners, the research team aspires to ultimately be able to design and build the next generation of anti-fungal compounds for applications in the agrochemical industry.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.