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

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With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. William Wuest from Emory University to investigate antifungal natural products active against blight. Blight is broadly defined as the disease or injury of plants marked by the formation of lesions, withering, or death of parts. Effects can range from widespread shortage of a specific crop to complete famine resulting in significant financial burden and societal hardships. In an effort to limit these potential threats, work presented in this research uses chemistry to make antifungal natural products and derivatives. Biological testing is also performed to evaluate their activity with the goal of creating new front-line agrochemicals. This pursuit allows graduate students to acquire specialized training in chemical synthesis and biological assays. This project additionally incorporates educational training for graduate student scientists interested in a diverse set of careers. Students are provided opportunities to participate in an innovative teaching program to diversify the workforce. Involvement in an educational program on consulting that leverages the existing entrepreneurial infrastructure at the university is also provided. The goal of this research project is to characterize and develop natural products and derivatives thereof for their implementation as inhibitors of agriculturally relevant pathogens. The target molecules are products found within the rhizosphere and have been exquisitely tuned to inhibit plant pathogens. Specifically, this project utilizes tools from synthetic organic chemistry, biochemistry, and microbiology to interrogate two specific natural products, promysalin and peniciaculin A. The compounds appear to act on plant pathogens as mimics of ubiquinone. Synthetic analogs are used to probe the molecular basis for the biological effects. By leveraging an understanding of the mechanistic targets of these natural products the research team is able to design and construct lead compounds for commercialization 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.