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

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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.