Systems biology of overflow metabolism
Vemuri, Goutham N.
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The primary goal of this research is to elucidate the regulation of overflow metabolism in Escherichia coli and Saccharomyces cerevisiae. Insufficient capacity of the respiratory pathways to oxidize NADH is hypothesized to be the cause of this phenomenon. Therefore, I increased NADH oxidation in these two organisms and studied the response from a systems biology perspective. I cloned NADH oxidase in E. coli as well as S. cerevisiae and observed a reduction in the overflow of acetate and glycerol, respectively, at the cost of biomass synthesis. I also introduced the cyanide-resistant alternate oxidation pathway in S. cerevisiae, which decreased ethanol production. Transcription profiling revealed interesting regulatory mechanisms, based on which I proposed new models for the control of overflow metabolism in these organisms. I believe that this research, spanning over three Universities (University of Georgia, University of Minnesota and Denmark Technical University), has laid the foundation for future redox-mediated metabolic engineering work in E. coli and S. cerevisiae.