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Effect of carbon source perturbations on transcriptional regulation of metabolic fluxes in Saccharomyces cerevisiae.
BMC Syst Biol. 2007 Mar 27; 1:18.BS

Abstract

BACKGROUND

Control effective flux (CEF) of a reaction is the weighted sum of all fluxes through that reaction, derived from elementary flux modes (EFM) of a metabolic network. Change in CEFs under different environmental conditions has earlier been proven to be correlated with the corresponding changes in the transcriptome. Here we use this to investigate the degree of transcriptional regulation of fluxes in the metabolism of Saccharomyces cerevisiae. We do this by quantifying correlations between changes in CEFs and changes in transcript levels for shifts in carbon source, i.e. between the fermentative carbon source glucose and nonfermentative carbon sources like ethanol, acetate, and lactate. The CEF analysis is based on a simple stoichiometric model that includes reactions of the central carbon metabolism and the amino acid metabolism.

RESULTS

The effect of the carbon shift on the metabolic fluxes was investigated for both batch and chemostat cultures. For growth on glucose in batch (respiro-fermentative) cultures, EFMs with no by-product formation were removed from the analysis of the CEFs, whereas those including any by-products (ethanol, glycerol, acetate, succinate) were omitted in the analysis of growth on glucose in chemostat (respiratory) cultures. This resulted in improved correlations between CEF changes and transcript levels. A regression correlation coefficient of 0.60 was obtained between CEF changes and gene expression changes in the central carbon metabolism for the analysis of 5 different perturbations. Out of 45 data points there were no more than 6 data points deviating from the correlation. Additionally, up- or down-regulation of at least 75% of the genes were in qualitative agreement with the CEF changes for all perturbations studied.

CONCLUSION

The analysis indicates that changes in carbon source are associated with a high degree of hierarchical regulation of metabolic fluxes in the central carbon metabolism as the change in fluxes are correlating directly with the change in transcript levels of genes encoding their corresponding enzymes. For amino acid biosynthesis there was, however, not found to exist a similar correlation, and this may point to either post-transcriptional and/or metabolic regulation, or be due to the absence of a direct perturbation on the amino acid pathways in these experiments.

Authors+Show Affiliations

Boğaziçi University, Department of Chemical Engineering, 34342, Bebek, Istanbul, Turkey. cakirtun@boun.edu.trNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17408508

Citation

Cakir, Tunahan, et al. "Effect of Carbon Source Perturbations On Transcriptional Regulation of Metabolic Fluxes in Saccharomyces Cerevisiae." BMC Systems Biology, vol. 1, 2007, p. 18.
Cakir T, Kirdar B, Onsan ZI, et al. Effect of carbon source perturbations on transcriptional regulation of metabolic fluxes in Saccharomyces cerevisiae. BMC Syst Biol. 2007;1:18.
Cakir, T., Kirdar, B., Onsan, Z. I., Ulgen, K. O., & Nielsen, J. (2007). Effect of carbon source perturbations on transcriptional regulation of metabolic fluxes in Saccharomyces cerevisiae. BMC Systems Biology, 1, 18.
Cakir T, et al. Effect of Carbon Source Perturbations On Transcriptional Regulation of Metabolic Fluxes in Saccharomyces Cerevisiae. BMC Syst Biol. 2007 Mar 27;1:18. PubMed PMID: 17408508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of carbon source perturbations on transcriptional regulation of metabolic fluxes in Saccharomyces cerevisiae. AU - Cakir,Tunahan, AU - Kirdar,Betül, AU - Onsan,Z Ilsen, AU - Ulgen,Kutlu O, AU - Nielsen,Jens, Y1 - 2007/03/27/ PY - 2006/10/09/received PY - 2007/03/27/accepted PY - 2007/4/6/pubmed PY - 2007/4/6/medline PY - 2007/4/6/entrez SP - 18 EP - 18 JF - BMC systems biology JO - BMC Syst Biol VL - 1 N2 - BACKGROUND: Control effective flux (CEF) of a reaction is the weighted sum of all fluxes through that reaction, derived from elementary flux modes (EFM) of a metabolic network. Change in CEFs under different environmental conditions has earlier been proven to be correlated with the corresponding changes in the transcriptome. Here we use this to investigate the degree of transcriptional regulation of fluxes in the metabolism of Saccharomyces cerevisiae. We do this by quantifying correlations between changes in CEFs and changes in transcript levels for shifts in carbon source, i.e. between the fermentative carbon source glucose and nonfermentative carbon sources like ethanol, acetate, and lactate. The CEF analysis is based on a simple stoichiometric model that includes reactions of the central carbon metabolism and the amino acid metabolism. RESULTS: The effect of the carbon shift on the metabolic fluxes was investigated for both batch and chemostat cultures. For growth on glucose in batch (respiro-fermentative) cultures, EFMs with no by-product formation were removed from the analysis of the CEFs, whereas those including any by-products (ethanol, glycerol, acetate, succinate) were omitted in the analysis of growth on glucose in chemostat (respiratory) cultures. This resulted in improved correlations between CEF changes and transcript levels. A regression correlation coefficient of 0.60 was obtained between CEF changes and gene expression changes in the central carbon metabolism for the analysis of 5 different perturbations. Out of 45 data points there were no more than 6 data points deviating from the correlation. Additionally, up- or down-regulation of at least 75% of the genes were in qualitative agreement with the CEF changes for all perturbations studied. CONCLUSION: The analysis indicates that changes in carbon source are associated with a high degree of hierarchical regulation of metabolic fluxes in the central carbon metabolism as the change in fluxes are correlating directly with the change in transcript levels of genes encoding their corresponding enzymes. For amino acid biosynthesis there was, however, not found to exist a similar correlation, and this may point to either post-transcriptional and/or metabolic regulation, or be due to the absence of a direct perturbation on the amino acid pathways in these experiments. SN - 1752-0509 UR - https://www.unboundmedicine.com/medline/citation/17408508/Effect_of_carbon_source_perturbations_on_transcriptional_regulation_of_metabolic_fluxes_in_Saccharomyces_cerevisiae_ L2 - https://bmcsystbiol.biomedcentral.com/articles/10.1186/1752-0509-1-18 DB - PRIME DP - Unbound Medicine ER -