A constraint-based model analysis of the metabolic consequences of increased NADPH oxidation in Saccharomyces cerevisiae

► A constraint-based model of yeast fermentation was developed and used to study NADPH homeostasis. ► The NADPH demand was increased to between 8 and 40-fold the anabolic demand. ► At moderate NADPH demand the PP and acetate pathways provide 80% and 20% of the NADPH demand. ► At high NADPH demand, the model predicts additional NADPH production from NADH by the glycerol-DHA futile cycle.