Optimal Strain Design for the Production of Ethanol from Renewable Biomass through Computing Elementary Flux Modes Using a Genome-Scale Stoichiometric Model
College: Agricultural, Consumer and Environmental Sciences
Award year: 2009-2010
Microbial cells have been utilized as a biocatalyst for conversion of biomass into value-added products. Metabolic phenotypes of naturally existing microorganisms are limited for various applications. Alternation of existing metabolic pathways or introduction of heterologous metabolic pathways for conferring beneficial phenotypes has been attempted. However, the metabolic phenotypes from the engineered microbial strains through metabolic engineering were often found to be suboptimal for commercialization, while successful in showing proof of the concept. The suboptimal phenotypes may be caused by uncharacterized interactions among metabolic pathways at the systems level upon perturbation of specific metabolic pathways. As such, we propose to employ a computational guide, enabling to predict global reconfigurations of genome-scale metabolic networks after specific genetic and environmental perturbations, for designing optimal strains for value added biotransformation. Specifically, we will focus on computing elementary flux modes (EFMs) from a medium-scale stoichiometric model in order to predict potential gene knockout targets improving yield of ethanol production from various sugars present in hydrolyzates of renewable biomass. A set of multiple knockout targets, eliminating the EFMs which are not favorable for high-yield ethanol production from the sugars, will be determined. Then, we will perform experimental validation for evaluating the effect of the identified knockouts on ethanol yields. Once the above mentioned strategy proves working, we will scale up the process using a genome-scale model through collaborations with NCSA scientists. The proposed study has both academic and industrial significances since the computation of EFMs from a genome scale metabolic model has not been reported and the outcomes of the proposed study, such as lists of knockout targets improving ethanol production, optimal ethanol producing strains, can be served as intellectual property.