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Background   Scheffersomyces stipitis  is a Crabtree negative yeast, commonly known for its capacity to ferment pentose sugars. Differently from Crabtree positive yeasts such as  Saccharomyces cerevisiae , the onset of fermentation in  S. stipitis  is not dependent on the sugar concentration, but is regulated by a decrease in oxygen levels. Even though  S. stipitis  has been extensively studied due to its potential application in pentoses fermentation, a limited amount of information is available about its metabolism during aerobic growth on glucose. Here, we provide a systems biology based comparison between the two yeasts, uncovering the metabolism of  S. stipitis  during aerobic growth on glucose under batch and chemostat cultivations.    Results  Starting from the analysis of physiological data, we confirmed through  13 C-based flux analysis the fully respiratory metabolism of  S. stipitis  when growing both under glucose limited or glucose excess conditions. The patterns observed showed similarity to the fully respiratory metabolism observed for  S. cerevisiae  under chemostat cultivations however, intracellular metabolome analysis uncovered the presence of several differences in metabolite patterns. To describe gene expression levels under the two conditions, we performed RNA sequencing and the results were used to quantify transcript abundances of genes from the central carbon metabolism and compared with those obtained with  S. cerevisiae . Interestingly, genes involved in central pathways showed different patterns of expression, suggesting different regulatory networks between the two yeasts. Efforts were focused on identifying shared and unique families of transcription factors between the two yeasts through  in silico  transcription factors analysis, suggesting a different regulation of glycolytic and glucoenogenic pathways.    Conclusions  The work presented addresses the impact of high-throughput methods in describing and comparing the physiology of Crabtree positive and Crabtree negative yeasts. Based on physiological data and flux analysis we identified the presence of one metabolic condition for  S. stipitis  under aerobic batch and chemostat cultivations, which shows similarities to the oxidative metabolism observed for  S. cerevisiae  under chemostat cultivations. Through metabolome analysis and genome-wide transcriptomic analysis several differences were identified. Interestingly,  in silico  analysis of transciption factors was useful to address a different regulation of mRNAs of genes involved in the central carbon metabolism. To our knowledge, this is the first time that the metabolism of  S. stiptis  is investigated in details and is compared to  S. cerevisiae . Our study provides useful results and allows for the possibility to incorporate these data into recently developed genome-scaled metabolic, thus contributing to improve future industrial applications of  S. stipitis  as cell factory.

Scheffersomyces stipitis: a comparative systems biology study with the Crabtree positive yeast Saccharomyces cerevisiae