17-31: Elucidation of redox balance in xylose fermentation with Pichia stipitis

It has been reported that the redox couples NAD+/NADH and NADP+/NADPH play important roles in energy metabolism and product formation in yeasts.  Specifically for Pichia stipitis, it has been reported that its ethanol yield is very sensitive to oxygen transfer rate due to redox imbalance.  Therefore, tuning up the redox conditions has significant impacts on ethanol production for P. stipitis, particularly for xylose fermentation.

In spite of the abundant experimental evidence regarding the role of redox balance in xylose utilization, there is a lack of understanding on the mechanism and cellular details of how redox imbalance affects the distribution of different metabolic products.  In this work, a constraint-based stoichiometric model of the central carbon metabolic network of Pichia stipitis is developed. The main metabolic reactions in glucose and xylose utilization by P. stipitis were incorporated in order to establish a stoichiometric reaction rate analysis of the network. In addition, flux variability analysis has been applied to the model to elucidate the redox balance of Pichia stipitis for xylose fermentation. The results revealed key metabolic constraints related to redox homeostasis.  A comparison of flux distribution involved in redox balance with different carbon sources and oxygenation conditions provides important insights on the role of redox balance in the metabolism of xylose utilization and ethanol production. Moreover, the interrelations between the NAD(H) and NADP(H) balances in P. stipitis were also studied.