Structural and mechanistic studies of oxalate catabolism

生物来源的草酸已被证明对作物生产和人类健康有负面影响。草酸盐是草酸的一种形式，是某些植物病原体感染所必需的。这些病原体每年都是造成重大作物损失的原因。草酸盐在植物性食物中的存在会降低它们的营养价值，也是一种潜在的毒素，有助于肾结石的形成。虽然草酸盐影响许多生物过程，但我们对其如何调节的理解有限。本项目将研究参与草酸调节的关键酶的结构和功能。这些研究将可能为促进植物代谢工程以提高其营养质量和植物源性食品的营养质量提供基础知识。这一研究项目也将广泛地纳入高中和本科生的科学培训课程。学生们将通过对项目的直接贡献获得宝贵的科研经验。外展活动亦会透过科学探索营扩展至本地6至12岁学生，以扩大他们对STEM的认识。草酸是由许多生物合成，以获得选择优势和提高他们的生存。考虑到草酸盐在自然界的广泛存在及其对许多生物的广泛影响，人们对这种重要酸的分解代谢知之甚少，这令人惊讶。草酸分解代谢的一个依赖辅酶A的途径最近被发现，并发现在植物和微生物中都起作用。本项目将确定拟南芥草酰辅酶a脱羧酶和两个候选拟南芥甲酰基辅酶a水解酶的结构和功能关系。这些酶被提议催化草酸分解代谢的辅酶a依赖途径的后续步骤。结构生物学，植物生物化学，遗传学和诱变方法将被用来阐明分子机制，并更好地了解这两个关键酶如何参与草酸分解代谢。该项目由生物科学理事会分子和细胞生物科学部的分子生物物理学计划资助。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。

Biologically derived oxalic acid has been shown to have a negative impact on crop production and human health. Oxalate, a form of oxalic acid, is required by certain plant pathogens for infection. Such pathogens are responsible for major crop losses every year. The presence of oxalate in plant foods can decrease their nutritional value and is also a potential toxin, contributing to kidney stone formation. Although oxalate impacts numerous biological processes, our understanding of how it is regulated is limited. This project will study the structure and function of key enzymes involved in the regulation of oxalate. These studies will potentially provide fundamental knowledge that will facilitate metabolic engineering of plants toward improving their nutritional quality and that of plant derived foods. This research project will also be broadly integrated into the curriculum for the training of high school and undergraduate students in science. The students will gain invaluable experience in scientific research through their direct contributions to the project. Outreach activities will also be extended to local 6 to12-year-old students through a science discovery camp to broaden their STEM exposure.Oxalic acid is biosynthesized by numerous organisms to gain a selective advantage and enhance their survival. Considering the widespread occurrence of oxalate in nature and its broad impact on a host of organisms, it is surprising that so little is known about the catabolism of this important acid. A CoA-dependent pathway of oxalate catabolism was recently discovered and found to function in both plants and microbes. This project will define the structure and function relationships of the Arabidopsis oxalyl-CoA decarboxylase and two candidate Arabidopsis formyl-CoA hydrolases. These enzymes are proposed to catalyze subsequent steps in the CoA-dependent pathway of oxalate catabolism. Structural biology, plant biochemistry, genetics, and mutagenesis approaches will be utilized to elucidate the molecular mechanisms and gain a better understanding of how these two key enzymes participate in oxalate catabolism. This project is funded by the Molecular Biophysics program of the Molecular and Cellular Biosciences Division in the Biological Sciences Directorate.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.