Structural and mechanistic studies of oxalate catabolism

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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.