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Scheffersomyces stipitis  is a yeast able to ferment pentoses to ethanol, unlike  Saccharomyces cerevisiae , it does not present the so-called overflow phenomenon. Metabolic features characterizing the presence or not of this phenomenon have not been fully elucidated. This work proposes that genome-scale metabolic response to variations in NAD(H/ + ) availability characterizes fermentative behavior in both yeasts. Thus, differentiating features in  S. stipitis  and  S. cerevisiae  were determined analyzing growth sensitivity response to changes in available reducing capacity in relation to ethanol production capacity and overall metabolic flux span. Using genome-scale constraint-based metabolic models, phenotypic phase planes and shadow price analyses, an excess of available reducing capacity for growth was found in  S. cerevisiae  at every metabolic phenotype where growth is limited by oxygen uptake, while in  S. stipitis  this was observed only for a subset of those phenotypes. Moreover, by using flux variability analysis, an increased metabolic flux span was found in  S. cerevisiae  at growth limited by oxygen uptake, while in  S. stipitis  flux span was invariant. Therefore, each yeast can be characterized by a significantly different metabolic response and flux span when growth is limited by oxygen uptake, both features suggesting a higher metabolic flexibility in  S. cerevisiae . By applying an optimization-based approach on the genome-scale models, three single reaction deletions were found to generate in  S. stipitis  the reducing capacity availability pattern found in  S. cerevisiae , two of them correspond to reactions involved in the overflow phenomenon. These results show a close relationship between the growth sensitivity response given by the metabolic network and fermentative behavior.

plos one

Genome-Scale NAD(H/+) Availability Patterns as a Differentiating Feature between Saccharomyces cerevisiae and Scheffersomyces stipitis in Relation to Fermentative Metabolism