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

开发受天然产物启发的泛醌模拟物作为下一代农用化学品

• 批准号: 2311665
• 负责人: William Wuest
• 金额: $ 64.03万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2311665&HistoricalAwards=false
• 关键词: Development; Natural; Product; Inspired; Ubiquinone

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.

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·韦斯特教授受到自然界产生的化合物的启发，正在开发新型农用化学品。枯萎病是一种导致大量作物死亡的疾病，主要由细菌和真菌引起。导致枯萎病的生物体不断进化，以抵抗农民使用的治疗方法，导致这些做法失败。因此，化学家需要不断寻找新的方法来维持目前的农业实践。已经确定了两种针对引起枯萎病的生物体的化合物，将使用化学方法和生物试验来验证所提出的假设。这些研究将为本科生和研究生提供发展有机合成专业技能的理想训练基地，并为他们在学术界或工业界的职业生涯做好准备。该项目还整合了两个专注于研究生职业发展的外展项目。第一个项目将为研究生提供课程设计方面的培训，同时向本科生讲授加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，专门培养研究生在创新、创业和咨询方面的能力。该研究项目旨在鉴定和开发天然产物及其衍生物，以作为农业相关病原体的抑制剂。重点将放在根际内发现的化合物，因为它们可能已经进化到特异性抑制植物病原体。该提案将使用多种方法，从合成有机化学到微生物学，来询问可能模仿天然辅因子泛醌的两个特定天然产物家族。具体而言，本研究的重点是青霉素激发的4-羟基吡啶酮天然产物的植物病原体抑制剂的合成和评价。通过与行业合作伙伴的合作，研究团队更好地了解了这些天然产物与其目标的关键相互作用，并希望最终能够设计和构建用于农化工业的下一代抗真菌化合物。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。