Functional characterization of the enzyme dipeptide interaction network and its role in the regulation of Arabidopsis carbon metabolism

新陈代谢驱动维持生命的化学反应，为植物的生长和功能提供能量和基础。该项目的目标是研究一类被称为二肽的小分子化合物如何控制植物中心碳代谢的活性。这项研究可能会导致以二肽为基础的改善植物适应性策略的创新，并可能产生可用于人类和动物健康的知识。该项目将为高中生、本科生和博士后提供研究培训。由于其快速和可逆的性质，关键酶活性的小分子调控对控制代谢通量至关重要。系统地识别调节代谢-酶相互作用仍然是代谢研究的重大挑战之一。本研究旨在系统表征新发现的模式植物拟南芥酶-二肽相互作用网络及其在调节中心碳代谢中的作用。为了阐明所研究的酶-二肽相互作用的代谢后果，该研究将利用体外双分子结合试验、酶活性表征、稳态代谢物水平的综合代谢组学分析以及二肽处理后的13C代谢通量分析相结合。这些分析的结果将与二肽积累模式重叠，以证明确定的相互作用的生理相关性。通过这个项目积累的基础知识将阐明生物学的一个核心问题：生物体在适应环境的过程中如何调节它们的新陈代谢。这项研究将描述一个隐藏的世界，其中大部分未被研究的酶-二肽相互作用，以及它们在蛋白质降解和代谢的关键调控关系中所起的作用。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。

Metabolism drives the life-sustaining chemical reactions that provide energy and building blocks for plant growth and function. The goal of this project is to investigate how a class of small-molecule compounds called dipeptides control the activity of the central carbon metabolism of plants. This research may lead to innovation in the form of dipeptide-based strategies for improving plant fitness and perhaps generate knowledge that can be used in human and animal health. This project will provide research training for high school students, undergraduate students and post-doctoral associates.Due to its rapid and reversible nature, small-molecule regulation of key enzymatic activities is vital to controlling metabolic fluxes. Systematic identification of regulatory metabolite-enzyme interactions remains one of the grand challenges in metabolism research. This research aims to systematically characterize the newly discovered enzyme-dipeptide interaction network and its role in regulating central carbon metabolism in the model plant Arabidopsis thaliana. To elucidate the metabolic consequences of the studied enzyme-dipeptide interactions, the research will exploit a combination of in vitro bimolecular binding assays, characterization of enzymatic activities, comprehensive metabolomic analysis of steady-state metabolite levels, and 13C metabolic flux analysis after dipeptide treatments. The results of these assays will be overlaid with dipeptide accumulation patterns to demonstrate the physiological relevance of the identified interactions. The basic knowledge accrued through this project will shed light on one of the central questions in biology: how organisms regulate their metabolism as they adapt to the environment. The research will characterize a hidden world of largely uninvestigated enzyme-dipeptide interactions, as well as their role in the critical yet poorly understood regulatory nexus of protein degradation and metabolism.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.