THE EXTRAORDINARY CONNECTIONS BETWEEN FLAVONOL AND BENZOATE METABOLISM

该项目的目标是阐明植物和一些细菌如何降解某些化学物质，称为黄酮醇，并使用相应的分解产物来制造关键分子。此类分子包括抗氧化剂和抗微生物化合物以及光合作用、呼吸作用、维生素生物合成和生物聚合物组装所需的化合物。该项目还将开创合成生物学策略，旨在操纵植物中的黄酮醇化学。所获得的知识将有利于作物的工程和育种，以抵抗生物和非生物胁迫，提高光合效率和化学惰性生物聚合物的碳固存。由于该研究依赖于多学科的专业知识，结合计算，遗传学和化学，该项目将为学生和博士后研究人员提供机会，以促进他们在生物技术行业和学术界目前高度需求的广泛技能方面的职业发展。该项目还包括一项旨在提高中学年龄儿童营养意识的推广计划。最近的研究表明，黄酮醇的过氧化反应会产生各种苯甲酸酯，植物--可能还有一些细菌--已经捕获了这种化学物质，从而创造出代谢节点，促进重要芳香前体的生物合成。来自比较基因组学、基因网络建模和生物化学遗传学的证据表明，过氧化物酶、糖基转移酶、β-糖苷酶和以前未表征的可溶性代谢物载体是这些过程的核心。该项目旨在识别此类酶和载体，确定它们的底物和亚细胞定位，以及植物如何使用相应的步骤来控制某些芳香代谢物的生物合成输出。该项目将联合收割机结合转录组和远缘系统谱系基因组的交叉检查，代谢重建，反向遗传学，靶代谢物的重同位素标记，酶学表征和共聚焦显微镜：1）揭示植物和原核生物中连接黄酮醇与芳香化合物生物合成途径的代谢节点。2)确定和表征控制黄酮醇过氧化的酶。3)阐明黄酮醇催化剂的产物如何在植物细胞内运输。该奖项反映了NSF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。

The goal of this project is to elucidate how plants and some bacteria degrade certain chemicals, called flavonols, and use the corresponding breakdown products to make crucial molecules. Such molecules include antioxidants and antimicrobial compounds as well as compounds required for photosynthesis, respiration, vitamin biosynthesis and biopolymer assembly. The project will also pioneer synthetic biology strategies that aim to manipulate flavonol chemistry in plants. The gained knowledge will benefit the engineering and breeding of crops for biotic and abiotic stress resistance, improved photosynthetic efficiency and carbon sequestration in chemically inert biopolymers. Since the research rests on a multidisciplinary expertise, combining computing, genetics, and chemistry, the project will provide opportunities to students and postdoctoral researchers to further their career development in a broad range of skills currently in high demand in the biotech industry and academia. This project also includes an outreach program aimed at raising nutritional awareness in children of middle school age.Recent research shows that the peroxidation of flavonols generates a variety of benzoates, and that plants –and likely some bacteria– have captured this chemistry to create metabolic nodes towards the biosynthesis of vital aromatic precursors. Converging evidence from comparative genomics, gene network modeling and biochemical genetics indicates that peroxidases, glycosyltransferases, β-glycosidases, and previously uncharacterized soluble metabolite carriers are central to these processes. The project aims to identify such enzymes and carriers, determine what their substrates and subcellular localizations are, and how plants use the corresponding steps to control the biosynthetic output of some aromatic metabolites. The project will combine the cross examination of transcriptomes and genomes of distant phylogenetic lineages with metabolic reconstructions, reverse genetics, heavy isotope labeling of target metabolites, enzymological characterization, and confocal microscopy to: 1) Uncover the metabolic nodes that connect flavonols to the biosynthetic pathways of aromatic compounds in plants and prokaryotes. 2) Identify and characterize the enzymes that control the peroxidation of flavonols. 3) Elucidate how the products of flavonol catabolism are transported inside plant cells.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.