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Computational Analysis of Yeast Xylose Metabolism

Ljubisa Miskovic and Vassily Hatzimanikatis. Laboratory of Computational Systems Biotechnology, Ecole Polytechnique Federale de Lausanne (EPFL), BCH 3111 (Bātiment de chimie UNIL), CH - 1015, Lausanne, Switzerland

Xylose fermentation from lignocellulosic material using recombinant yeast cells is a promising resource for efficient ethanol production as a future sustainable energy supply. Experimental approaches emphasize the engineering of xylose-utilizing recombinant Saccharomyces cerevisiae strains to overcome the potential bottlenecks of xylose uptake and cofactor imbalance and to minimize the xylitol accumulation. In this work, we apply systems engineering methodology in order to identify metabolic engineering targets for the optimization of ethanol production by Saccharomyces cerevisiae in the continuous culture. We employ a computational framework we have recently developed for Metabolic Control Analysis, i.e., the quantification of the responses of metabolic properties to changes in genetic manipulations and environmental (process) conditions. We find that redistribution of the metabolic flows around pyruvate among carboxylation, decarboxylation, and transport has significant potential in improving total utilization of hexose and pentose sugar as well as its conversion into ethanol. We also find such objective may be achieved with a more efficient ATP molecule dissipation through maintenance demand and respiration.