초록
<P><I>Scheffersomyces stipitis</I> is a yeast able to ferment pentoses to ethanol, unlike <I>Saccharomyces cerevisiae</I>, 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/<SUP>+</SUP>) availability characterizes fermentative behavior in both yeasts. Thus, differentiating features in <I>S. stipitis</I> and <I>S. cerevisiae</I> 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 <I>S. cerevisiae</I> at every metabolic phenotype where growth is limited by oxygen uptake, while in <I>S. stipitis</I> this was observed only for a subset of those phenotypes. Moreover, by using flux variability analysis, an increased metabolic flux span was found in <I>S. cerevisiae</I> at growth limited by oxygen uptake, while in <I>S. stipitis</I> 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 <I>S. cerevisiae</I>. By applying an optimization-based approach on the genome-scale models, three single reaction deletions were found to generate in <I>S. stipitis</I> the reducing capacity availability pattern found in <I>S. cerevisiae</I>, 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.</P>