Rice: Unconventional Wisdom
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Metabolic Engineering and Synthetic & Systems Biology Laboratory

Metabolism of 5- and 6-C Sugar Mixtures in E. coli

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The sugar platform is based on extracting sugars from plant biomass and using them as substrates (feedstocks) for the production of fuels and chemicals, predominantly via fermentation processes. Our efforts in this area concentrate on the understanding and engineering of E. coli sugar-utilization regulatory systems for the consumption of plant biomass sugars.

Although well established for cornstarch-derived sugars like glucose, the fermentation of 5- and 6-carbon sugar mixtures obtained from cellulosic biomass remains challenging (i.e., higher capital and operational costs). Our initial work in this area was motivated by the need to address these issues. For example, while the initial goal of simultaneous consumption of 5- and 6-carbon sugar has been achieved, engineered strains do not exhibit significant kinetic advantages over wild-type sequential metabolism of sugars. We are studying the implications of simultaneous vs. sequential metabolism of 5- and 6-C sugars on cellular metabolism, metabolic fluxes, and regulation. We are addressing fundamental questions such as what limits the glycolytic flux or whether cells engineered to simultaneously consume multiple sugars would be able to handle the resulting “excess” glycolytic flux. We are using a systems biology-based approach that takes advantage of the most recent advances in experimental tools in the area of functional genomics (e.g., DNA microarrays, labeling experiments-based estimation of metabolic fluxes, etc.) as well as new developments in system-wide mathematical/statistical tools for the analysis of these systems. To this end we have made significant contributions in both methodologies and fundamental understanding of the system. For example, we have developed: (1) a superior method for estimating metabolic fluxes using 13C labeling experiments, (2) a novel PCA-based method for the identification of assay-specific signatures in functional genomic studies, (3) a novel tool (Elementary Network Decomposition, END) to help elucidate the network topology of regulatory systems. These tools and methodologies have been successfully used in the study of the sugar-utilization regulatory systems in E. coli. Our future work in this area will continue to address issues related to the optimum utilization of sugar mixtures along with other topics relevant to the production of fuels and chemicals from biomass hydrolysates.