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

在化学系生命过程中的化学项目的支持下，埃默里大学的威廉·威斯特教授正在开发受自然界中产生的化合物启发的新型农用化学品。枯萎病是一种导致大量农作物死亡的疾病，主要由细菌和真菌引起。导致枯萎病的微生物不断进化，以抵抗农民使用的治疗方法，导致这些做法失败。因此，化学家将需要不断地寻找新的方法来维持当前的农业实践。已经确定了两种化合物作为致病微生物的靶标，并将使用化学方法和生物测试来验证所提出的假设。这些研究将为本科生和研究生提供一个发展有机合成专业技能的理想培训基础，并将为他们在学术界或工业中的职业生涯做好准备。该项目还整合了两个以研究生职业发展为重点的外展项目。第一个项目将为研究生提供课程设计方面的培训，同时向本科生传授进入大学研究实验室的过程。第二个项目通过参与埃默里生物技术咨询俱乐部提供的活动，对研究生进行创新、创业和咨询方面的专门培训。研究项目旨在表征和开发天然产品及其衍生物，以便将其作为农业相关病原体的抑制剂实施。重点将放在根际发现的化合物上，因为它们可能已经进化成专门抑制植物病原体的。这项提案将使用从合成有机化学到微生物学的各种方法来询问两个特定的天然产品家族，它们可能模仿天然辅因子泛醌。具体地说，本研究的重点是4-羟基吡啶酮类天然产物中青霉素类植物病原菌抑制剂的合成和评价。随着更好地了解这些天然产品与其目标的关键相互作用，并通过与行业合作伙伴的合作，研究团队渴望最终能够设计和制造用于农化行业的下一代抗真菌化合物。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.