Dataset Information

Integration of transcription and flux data reveals molecular paths associated with differences in oxygen-dependent phenotypes of Saccharomyces cerevisiae.

ABSTRACT:

Background

Saccharomyces cerevisiae is able to adapt to a wide range of external oxygen conditions. Previously, oxygen-dependent phenotypes have been studied individually at the transcriptional, metabolite, and flux level. However, the regulation of cell phenotype occurs across the different levels of cell function. Integrative analysis of data from multiple levels of cell function in the context of a network of several known biochemical interaction types could enable identification of active regulatory paths not limited to a single level of cell function.

Results

The graph theoretical method called Enriched Molecular Path detection (EMPath) was extended to enable integrative utilization of transcription and flux data. The utility of the method was demonstrated by detecting paths associated with phenotype differences of S. cerevisiae under three different conditions of oxygen provision: 20.9%, 2.8% and 0.5%. The detection of molecular paths was performed in an integrated genome-scale metabolic and protein-protein interaction network.

Conclusions

The molecular paths associated with the phenotype differences of S. cerevisiae under conditions of different oxygen provisions revealed paths of molecular interactions that could potentially mediate information transfer between processes that respond to the particular oxygen availabilities.

SUBMITTER: Lindfors E

PROVIDER: S-EPMC3930817 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Publications

Integration of transcription and flux data reveals molecular paths associated with differences in oxygen-dependent phenotypes of Saccharomyces cerevisiae.

Lindfors Erno E Jouhten Paula P Oja Merja M Rintala Eija E Orešič Matej M Penttilä Merja M

BMC systems biology 20140214

<h4>Background</h4>Saccharomyces cerevisiae is able to adapt to a wide range of external oxygen conditions. Previously, oxygen-dependent phenotypes have been studied individually at the transcriptional, metabolite, and flux level. However, the regulation of cell phenotype occurs across the different levels of cell function. Integrative analysis of data from multiple levels of cell function in the context of a network of several known biochemical interaction types could enable identification of a ...[more]

PMID: 24528924

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Project description:BackgroundTo engineer Saccharomyces cerevisiae for efficient xylose utilization, a fungal pathway consisting of xylose reductase, xylitol dehydrogenase, and xylulose kinase is often introduced to the host strain. Despite extensive in vitro studies on the xylose pathway, the intracellular metabolism rewiring in response to the heterologous xylose pathway remains largely unknown. In this study, we applied 13C metabolic flux analysis and stoichiometric modeling to systemically investigate the flux distributions in a series of xylose utilizing S. cerevisiae strains.ResultsAs revealed by 13C metabolic flux analysis, the oxidative pentose phosphate pathway was actively used for producing NADPH required by the fungal xylose pathway during xylose utilization of recombinant S. cerevisiae strains. The TCA cycle activity was found to be tightly correlated with the requirements of maintenance energy and biomass yield. Based on in silico simulations of metabolic fluxes, reducing the cell maintenance energy was found crucial to achieve the optimal xylose-based ethanol production. The stoichiometric modeling also suggested that both the cofactor-imbalanced and cofactor-balanced pathways could lead to optimal ethanol production, by flexibly adjusting the metabolic fluxes in futile cycle. However, compared to the cofactor-imbalanced pathway, the cofactor-balanced xylose pathway can lead to optimal ethanol production in a wider range of fermentation conditions.ConclusionsBy applying 13C-MFA and in silico flux balance analysis to a series of recombinant xylose-utilizing S. cerevisiae strains, this work brings new knowledge about xylose utilization in two aspects. First, the interplays between the fungal xylose pathway and the native host metabolism were uncovered. Specifically, we found that the high cell maintenance energy was one of the key factors involved in xylose utilization. Potential strategies to reduce the cell maintenance energy, such as adding exogenous nutrients and evolutionary adaptation, were suggested based on the in vivo and in silico flux analysis in this study. In addition, the impacts of cofactor balance issues on xylose utilization were systemically investigated. The futile pathways were identified as the key factor to adapt to different degrees of cofactor imbalances and suggested as the targets for further engineering to tackle cofactor-balance issues.

Dataset Information

Integration of transcription and flux data reveals molecular paths associated with differences in oxygen-dependent phenotypes of Saccharomyces cerevisiae.

Background

Results

Conclusions

Publications

Integration of transcription and flux data reveals molecular paths associated with differences in oxygen-dependent phenotypes of Saccharomyces cerevisiae.

Similar Datasets

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