A SYSTEMS BIOLOGY APPROACH TO UNCOVERING THE HIDDEN REDOX REACTIONS OF PLANT AND BACTERIAL METABOLISM

该项目旨在识别和工程植物和微生物酶，这些酶是生产有益分子所必需的，如维生素，膳食抗氧化剂和参与光合作用或防御害虫的植物化合物。这项研究将为植物育种者和代谢工程师创造新的目标，他们寻求利用自然化学来提高作物价值、营养质量和生产力。由于该项目结合了生物学，化学和计算方面的多学科专业知识，因此它将为学生和博士后研究人员提供机会，以促进他们在广泛技能和兴趣方面的职业发展。这种跨学科的培训在学术界，私营企业和政府中的需求很高。该项目还包括一个旨在提高中学生及其父母营养意识的试点推广计划。试点调查表明，许多重要芳香族化合物的氧化还原状态决定了它们在体内的最终甲基化和/或进一步内酯化（环化），植物和细菌已经捕获了这种化学物质，在其代谢网络中创建了调节节点。专用的氧化还原酶，迄今为止仍然隐藏在传统的生物化学和遗传学方法，似乎是这些过程的核心。该项目旨在识别和表征此类酶，确定产氧光合生物如何使用相应的反应来控制其一些芳香代谢产物的生物合成输出，并使用所获得的知识来设计同源途径。具体而言，该项目将结合联合收割机比较基因组学、基因网络建模和生物化学遗传学：1）鉴定参与代谢物甲基化和内酯化的真核和原核氧化还原酶; 2）在体外和体内表征氧化还原的相应反应，并将所得的功能注释和代谢重建传播到参考基因组、代谢和酶数据库; 3）构建保护氧化还原活性芳族中间体免于自发再氧化的合成代谢子。该项目由分子和细胞生物科学部的系统和合成生物学计划资助。

This project aims to identify and engineer plant and microbial enzymes that are required for the production of beneficial molecules like vitamins, dietary antioxidants, and plant compounds that participate in photosynthesis or defense against pests. This research will generate novel targets for plant breeders and metabolic engineers who seek to increase crop value, nutritional quality, and productivity using the chemistry of nature. Because this project combines multidisciplinary expertise in biology, chemistry, and computing, it will provide opportunities to students and postdoctoral researchers to further their career development in a broad range of skills and interests. This cross-disciplinary training is in high-demand in academia, private industry and in government. This project also includes a pilot outreach program aimed at raising nutritional awareness in children of middle school age and their parents.Pilot investigations suggest that the redox state of a number of vital aromatic compounds determines their eventual methylation and/or further lactonization (cyclization) in vivo, and that plants and bacteria have captured this chemistry to create regulatory nodes in their metabolic networks. Dedicated oxidoreductases, which have so far remained hidden to conventional biochemical and genetics approaches, appear to be central to these processes. This project aims to identify and characterize such enzymes, determine how oxygenic photosynthetic organisms use the corresponding reactions to control the biosynthetic output of some of their aromatic metabolites, and use the gained knowledge to engineer the cognate pathways. Specifically, the project will combine comparative genomics, gene network modeling, and biochemical genetics to: 1) Identify eukaryotic and prokaryotic oxidoreductases involved in the methylation and the lactonization of metabolites; 2) Characterize the corresponding reactions of oxidoreduction in vitro and in vivo, and propagate the resulting functional annotations and metabolic reconstructions to reference genomic, metabolic and enzymes databases; 3) Build synthetic metabolons that protect redox active aromatic intermediates from spontaneous re-oxidation. This project is funded by the Systems and Synthetic Biology Program in the Division of Molecular and Cellular Biosciences.