THE EXTRAORDINARY CONNECTIONS BETWEEN FLAVONOL AND BENZOATE METABOLISM

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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.