Thiol-based redox switch in plant flavonoid biosynthesis

植物类黄酮生物合成中的硫醇基氧化还原开关

• 批准号: 1709616
• 负责人: Jing-Ke Weng
• 金额: $ 42万
• 依托单位: Whitehead Institute for Biomedical Research
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709616&HistoricalAwards=false
• 关键词: Thiol; based; redox; switch; plant

The Chemistry of Life Processes Program in the Chemistry Division funds this award. Dr. Jing-Ke Weng from the Whitehead Institute for Biomedical Research investigates the impact of a chemical reactions with oxygen in regulating a plant enzyme. All land plants produce a class of molecules called flavonoids, using the enzyme known as chalcone synthase. Flavonoids are important for plants to survive on land and play many roles such as protection against ultraviolet light, defense against herbivores, and attraction of pollinators. Using high resolution techniques for the determination of structure, chalcone synthase was observed to have evolved a regulatory switch that affects its activity when it reacts with oxygen. By comparing chalcone synthase from a variety of plants such as simple land plants to flowering plants, this research helps characterize how flavonoid biosynthesis has evolved to help plants adapt to life in a wide variety of terrestrial habitats. This knowledge has the potential to improve plant traits in the future. This project allows graduate students to acquire hands-on training in multidisciplinary cutting-edge techniques. This project also integrates middle-school and high-school outreach programs to introduce students to plant physiology and chemistry. Oxidation of the cysteinyl side chain in proteins occurs widely in all living organisms, often as a result of increased levels of reactive oxygen species (ROS). The goal of this research is to gain a mechanistic understanding of how the activity of chalcone synthase (CHS), the first committed enzyme in plant flavonoid biosynthesis, is controlled by oxidative inactivation of its catalytic cysteine at both the enzyme and systems levels. CHS orthologs from diverse land plant lineages are characterized in vitro using X-ray crystallography and enzyme activity assays to examine how the redox potential of the catalytic cysteine is impacted by nearby amino acid differences between orthologs. In vivo studies involving metabolic tracing and proteomics on transgenic Arabidopsis thaliana expressing different CHS orthologs and subjected to various oxidative stress conditions examine the impact of CHS oxidation on flavonoid biosynthesis, and provide insight into its functional impact on the evolution of land plants. Because CHSs are homologous to, and evolutionarily derived from, the beta-ketoacyl-(acyl-carrier-protein) synthases, the proposed research has far-reaching impact for understanding how fatty acid biosynthesis may be influenced by fluctuating cellular redox status, which is an underexplored research topic relevant to diverse disciplines, e.g. oil production in seed crops under stress conditions.

化学部的生命过程化学计划资助该奖项。怀特海德生物医学研究所的翁景科博士研究了与氧气的化学反应对调节植物酶的影响。所有陆地植物都会使用称为查尔酮合酶的酶产生一类称为类黄酮的分子。黄酮类化合物对于植物在陆地上的生存非常重要，并发挥多种作用，例如抵御紫外线、防御食草动物和吸引传粉者。使用高分辨率技术确定结构，观察到查尔酮合酶进化出了一个调节开关，当它与氧气反应时，会影响其活性。通过比较各种植物（例如简单的陆地植物和开花植物）的查尔酮合酶，这项研究有助于描述类黄酮生物合成如何进化，以帮助植物适应各种陆地生境的生活。这些知识有可能在未来改善植物性状。该项目使研究生能够获得多学科尖端技术的实践培训。该项目还整合了初中和高中的推广计划，向学生介绍植物生理学和化学。蛋白质中半胱氨酰侧链的氧化在所有生物体中广泛发生，通常是由于活性氧 (ROS) 水平增加的结果。本研究的目的是从机制上了解查尔酮合酶 (CHS) 的活性如何通过其催化半胱氨酸在酶和系统水平上的氧化失活来控制，CHS 是植物类黄酮生物合成中的第一个关键酶。使用 X 射线晶体学和酶活性测定对来自不同陆地植物谱系的 CHS 直向同源物进行体外表征，以检查直向同源物之间附近氨基酸差异如何影响催化半胱氨酸的氧化还原电位。体内研究涉及表达不同 CHS 直系同源物并经受各种氧化应激条件的转基因拟南芥的代谢追踪和蛋白质组学，检查 CHS 氧化对类黄酮生物合成的影响，并深入了解其对陆地植物进化的功能影响。由于 CHS 与 β-酮酰基-（酰基载体蛋白）合酶同源，并且在进化上源自β-酮酰基-（酰基载体蛋白）合酶，因此拟议的研究对于理解脂肪酸生物合成如何受到细胞氧化还原状态波动的影响具有深远的影响，这是一个与不同学科相关的尚未充分探索的研究主题，例如生物化学。胁迫条件下种子作物的石油生产。

项目成果

Plant Solutions for the COVID-19 Pandemic and Beyond: Historical Reflections and Future Perspectives

• DOI: 10.1016/j.molp.2020.05.014
• 发表时间: 2020-05
• 期刊: Molecular Plant
• 影响因子: 27.5
• 作者: J. Weng

Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins

• DOI: 10.1073/pnas.1920097117
• 发表时间: 2020-05-19
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Torrens-Spence, Michael P.;Chiang, Ying-Chih;Weng, Jing-Ke
• 通讯作者: Weng, Jing-Ke

PBS3 and EPS1 Complete Salicylic Acid Biosynthesis from Isochorismate in Arabidopsis

• DOI: 10.1016/j.molp.2019.11.005
• 发表时间: 2019-12-02
• 期刊: MOLECULAR PLANT
• 影响因子: 27.5
• 作者: Torrens-Spence, Michael P.;Bobokalonova, Anastassia;Weng, Jing-Ke
• 通讯作者: Weng, Jing-Ke

PRX9 and PRX40 Are Extensin Peroxidases Essential for Maintaining Tapetum and Microspore Cell Wall Integrity during Arabidopsis Anther Development

• DOI: 10.1105/tpc.18.00907
• 发表时间: 2019-04-01
• 期刊: PLANT CELL
• 影响因子: 11.6
• 作者: Jacobowitz, Joseph R.;Doyle, William C.;Weng, Jing-Ke
• 通讯作者: Weng, Jing-Ke

The biosynthetic origin of psychoactive kavalactones in kava

• DOI: 10.1038/s41477-019-0474-0
• 发表时间: 2019-08-01
• 期刊: NATURE PLANTS
• 影响因子: 18
• 作者: Pluskal, Tomas;Torrens-Spence, Michael P.;Weng, Jing-Ke
• 通讯作者: Weng, Jing-Ke