Elucidating xylose metabolism of scheffersomyces stipitis by integrating principal component analysis with flux balance analysis

The conversion of pentose to ethanol is one of the major barriers of industrializing lignocellulosic ethanol processes. As the most promising native strain for pentose fermentation, Scheffersomyces stipitis (formerly known as Pichia stipitis) has been widely studied for its xylose fermentation. In spite of the abundant experimental evidence regarding ethanol and by-products production under various aeration conditions, the mathematical descriptions of the processes are rare. In this work, the constraint-based metabolic network model for the central carbon metabolism of S. stipitis was reconstructed by integrating genomic (P. stipitis v2.0, KEGG), biochemical (ChEBI, KEGG) and physiological information available for this microorganisms and other related yeast. The model consists of the stoichiometry of metabolic reactions, the biosynthetic requirements for growth and other constraints. Flux Balance Analysis is applied to characterize the phenotypic behavior of S. stipitis grown on xylose. The model predictions are in good agreement with published experimental results. In addition, a series of specially designed in silico experiments are performed, and PCA has been applied to analyze the results to elucidate the redox balance of S. stipitis for xylose fermentation. The analysis revealed key metabolic reactions related to redox homeostasis and could provide important insights on cofactor engineering of xylose metabolism.