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

通过这一奖项，化学部的生命过程化学计划资助埃默里大学的威廉·威斯特博士研究抗真菌天然产品，以对抗枯萎病。枯萎病被广泛定义为植物的疾病或伤害，其特征是形成病变、枯萎或部分死亡。影响的范围可能从某一特定作物的普遍短缺到造成重大财政负担和社会困难的完全饥荒。为了限制这些潜在的威胁，这项研究中提出的工作使用化学来制造抗真菌的天然产品和衍生品。还进行了生物测试，以评估它们的活性，目的是创造新的一线农用化学品。这一追求使研究生能够获得化学合成和生物分析方面的专门培训。该项目还包括对对不同职业感兴趣的研究生科学家的教育培训。为学生提供参加创新教学计划的机会，以实现劳动力多样化。还提供了一个利用大学现有创业基础设施的咨询教育方案的参与。这一研究项目的目标是表征和开发天然产品及其衍生物，以便将其用作农业相关病原体的抑制剂。目标分子是在根际环境中发现的产物，经过精心调整，可以抑制植物病原体。具体地说，这个项目利用合成有机化学、生物化学和微生物学的工具来询问两种特定的天然产物，丙杨素和青霉素A。这两种化合物似乎作为泛醌的模拟物对植物病原体起作用。合成的类似物被用来探索生物效应的分子基础。通过利用对这些天然产品的机械目标的了解，研究团队能够设计和制造用于农化工业商业化的先导化合物。这一奖项反映了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 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.