Application of systems biology tools to understand the effect of acetic acid on ethanol production by Saccharomyces cerevisiae 424A(LNH-ST)

A significant challenge facing the cellulosic ethanol industry is the availability of robust industrial microbes that are capable of mixed sugar fermentation with tolerance to inhibitors. One such inhibitor is acetic acid, a compound released from the cellulosic biomass during pretreatment. Engineering an organism for improved inhibitor tolerance requires a fundamental understanding of the effect of acetic acid at a cellular level.;This dissertation evaluated the effect of acetic acid on the co-fermentation of glucose and xylose to ethanol using two approaches. (1) A kinetic model for the co-fermentation of glucose and xylose by S. cerevisiae 424A(LNH-ST) was developed to estimate important fermentation performance parameters. The resulting model showed acetic acid had a severe inhibitory impact on xylose fermentation. (2) The systems biology tools transcriptomics and metabolomics were used to determine the effect of acetic acid on gene expression levels and intracellular metabolite concentrations. Results showed that acetic acid does not have a singular inhibition mechanism, instead it was found to impact a variety of cellular processes.