CAREER: Determining the Metabolic Organization and Enzymology of the Fundamentally Important Flavonoid Biosynthetic Pathway

职业：确定基本重要的类黄酮生物合成途径的代谢组织和酶学

• 批准号: 2045182
• 负责人: Daniel Owens
• 金额: $ 87.62万
• 依托单位: University of Hawaii
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2045182&HistoricalAwards=false
• 关键词: CAREER; Determining; Metabolic; Organization; Enzymology

Metabolism, or the set of chemical reactions that occur inside cells that sustain life, is typically represented in a linear fashion, with inputs and outputs of each reaction considered independent of the spatial arrangement of enzymes that govern those reactions. A primary objective of this work is to expand the view of metabolism beyond current linear two-dimensional models to more holistic three-dimensional representations. A metabolon is a group of enzymes that organize in three dimensions by interacting together to generate a “machine” that can direct flow and influence the path through the overall system. Determining metabolon formation provides fundamental information on how different compounds are produced in living organisms and gives insight into how to manipulate these systems to improve the production of compounds of interest. This work focuses on using orange (Citrus sinensis) to determine metabolon organization of the flavonoid biosynthetic pathway, which can be utilized for human benefit. The Broader Impact of this works includes the intrinsic nature of the research on flavonoids, which have important health and nutritional qualities. Additional work with students will include opportunities to become involved in the research itself and outreach efforts will teach students how to grow their own food. The activities will include a focused effort to include Pacific Islanders who are underrepresented in science. It is hoped these activities will capture the interest of young people due to the hands-on components and expose them to mentors who are currently successful in science and agriculture.The overall research objective for this project is to determine the metabolic organization and enzymology of the flavonoid biosynthetic pathway in orange. The central hypothesis is that accumulation of flavonoid end products in orange depends upon formation of a metabolon. The rationale for the proposed research is that a determination of the enzymology and metabolic organization of the orange flavonoid biosynthetic pathway will identify targets for improving the content and quality of flavonoid metabolites for applications beneficial to humanity. These objectives will be achieved by identifying structure-function relationships of metabolon enzymes involved in biosynthesis of orange flavonoids, and determine the organization of enzymes comprising flavonoid metabolons of blonde and blood varieties of orange. The work expands from prior use of the model system Arabidopsis thaliana by employing the fundamentally and agriculturally important species orange, which allows analysis of differences in metabolon formation between species that accumulate early and late flavonoids. Glycosyltransferase enzymes will also be studied as they contribute to the production of the majority of flavonoid compounds which accumulate in vivo but are currently understudied.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.

新陈代谢，或维持生命的细胞内发生的一系列化学反应，通常以线性方式表示，每个反应的输入和输出被认为独立于控制这些反应的酶的空间排列。这项工作的主要目标是将新陈代谢的观点从目前的线性二维模型扩展到更全面的三维表示。代谢物是一组酶，它们通过相互作用在三维空间中组织起来，产生一个“机器”，可以指导流动并影响整个系统的路径。确定代谢形成提供了关于不同化合物如何在生物体中产生的基本信息，并深入了解如何操纵这些系统以提高感兴趣的化合物的产生。本研究主要利用柑橘（Citrus sinensis）来确定类黄酮生物合成途径的代谢组织，从而为人类提供有益的利用。这项工作的更广泛的影响包括黄酮类化合物研究的内在性质，它具有重要的健康和营养品质。与学生一起的额外工作将包括参与研究本身的机会，以及外联工作将教学生如何种植自己的食物。这些活动将包括一项重点努力，包括在科学领域代表性不足的太平洋岛民。希望这些活动能够通过动手的部分吸引年轻人的兴趣，并让他们接触到目前在科学和农业领域取得成功的导师。本项目的总体研究目的是确定橙子类黄酮生物合成途径的代谢组织和酶学。中心的假设是，黄酮类化合物的最终产物在橙子的积累取决于代谢的形成。本研究的基本原理是确定橙子类黄酮生物合成途径的酶学和代谢组织，将确定提高类黄酮代谢物含量和质量的目标，以造福人类。通过对橙子黄酮生物合成中代谢酶的结构-功能关系的研究，以及对黄酮代谢酶的组织结构的研究，将有助于实现上述目标。这项工作在先前使用拟南芥模型系统的基础上进行了扩展，采用了基础和农业上重要的物种橙子，这使得分析了积累早期和晚期黄酮类化合物的物种之间代谢形成的差异。糖基转移酶也将被研究，因为它们有助于大多数类黄酮化合物的产生，这些化合物在体内积累，但目前尚未得到充分研究。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。