Skip to main content
SpringerLink
Log in

Quantification of metabolism in Saccharomyces cerevisiae under hyperosmotic conditions using elementary mode analysis

  • Systems Biotechnology
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Yeast metabolism under hyperosmotic stress conditions was quantified using elementary mode analysis to obtain insights into the metabolic status of the cell. The fluxes of elementary modes were determined as solutions to a linear program that used the stoichiometry of the elementary modes as constraints. The analysis demonstrated that distinctly different sets of elementary modes operate under normal and hyperosmotic conditions. During the adaptation phase, elementary modes that only produce glycerol are active, while elementary modes that yield biomass, ethanol, and glycerol become active after the adaptive phase. The flux distribution in the metabolic network, calculated using the fluxes in the elementary modes, was employed to obtain the flux ratio at key nodes. At the glucose 6-phosphate (G6P) node, 25% of the carbon influx was diverted towards the pentose phosphate pathway under normal growth conditions, while only 0.3% of the carbon flux was diverted towards the pentose phosphate pathway during growth at 1 M NaCl, indicating that cell growth is arrested under hyperosmotic conditions. Further, objective functions were used in the linear program to obtain optimal solution spaces corresponding to the different accumulation rates. The analysis demonstrated that while biomass formation was optimal under normal growth conditions, glycerol synthesis was closer to optimal during adaptation to osmotic shock.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Albertyn J, Hohmann S, Prior BA (1994) Characterization of the osmotic-stress response in Saccharomyces cerevisiae: osmotic stress and glucose repression regulate glycerol-3-phosphate dehydrogenase independently. Curr Genet 25(1):12–18

    Article  PubMed  CAS  Google Scholar 

  2. Blomberg A (1995) Global changes in protein synthesis during adaptation of the yeast Saccharomyces cerevisiae to 0.7 M NaCl. J Bacteriol 177(12):3563–3572

    Google Scholar 

  3. Blomberg A, Adler L (1989) Roles of glycerol and glycerol-3-phosphate dehydrogenase (NAD+) in acquired osmotolerance of Saccharomyces cerevisiae. J Bacteriol 171(2):1087–1092

    Google Scholar 

  4. Brewster J, de Valoir T, Dwyer N, Winter E, Gustin M (1993) An osmosensing signal transduction pathway in yeast. Science 259(5102):1760–1763

    Article  PubMed  CAS  Google Scholar 

  5. Çakir T, Kirdar B, Ülgen KÖ (2004) Metabolic pathway analysis of yeast strengthens the bridge between transcriptomics and metabolic networks. Biotechnol Bioeng 86(3):251–260

    Article  PubMed  Google Scholar 

  6. Carlson R, Fell D, Srienc F (2002) Metabolic pathway analysis of a recombinant yeast for rational strain development. Biotechnol Bioeng 79(2):121–134

    Article  PubMed  CAS  Google Scholar 

  7. Carlson R, Srienc F (2004) Fundamental Escherichia coli biochemical pathways for biomass and energy production: identification of reactions. Biotechnol Bioeng 85(1):1–19

    Google Scholar 

  8. Gayen K, Gupta M, Venkatesh KV (2007) Elementary mode analysis to study the preculturing effect on the metabolic state of Lactobacillus rhamnosus during growth on mixed substrates. In Silico Biol 7(2):123–139

    Google Scholar 

  9. Gayen K, Venkatesh KV (2006) Analysis of optimal phenotypic space using elementary modes as applied to Corynebacterium glutamicum. BMC Bioinform 7:445

    Article  Google Scholar 

  10. Gianchandani EP, Papin JA, Price ND, Joyce AR, Palsson BO (2006) Matrix formalism to describe functional states of transcriptional regulatory systems. PLoS Comput Biol 2(8):902–917

    Article  CAS  Google Scholar 

  11. Gustin MC, Albertyn J, Alexander M, Davenport K (1998) Map kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev 62(4):1264–1300

    PubMed  CAS  Google Scholar 

  12. Hohmann S (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev 66(2):300–372

    Article  PubMed  CAS  Google Scholar 

  13. Klamt S (2006) Generalized concept of minimal cut sets in biochemical networks. Biosystems 83(2–3):233–247

    Google Scholar 

  14. Klamt S, Gilles ED (2004) Minimal cut sets in biochemical reaction networks. Bioinformatics 20(2):226–234

    Article  PubMed  CAS  Google Scholar 

  15. Klamt S, Saez-Rodriguez J, Lindquist JA, Simeoni L, Gilles ED (2006) A methodology for the structural and functional analysis of signaling and regulatory networks. BMC Bioinform 7:1–26

    Article  Google Scholar 

  16. Klipp E, Nordlander B, Kruger R, Gennemark P, Hohmann S (2005) Integrative model of the response of yeast to osmotic shock. Nat Biotechnol 23(8):975–982

    Article  PubMed  CAS  Google Scholar 

  17. Lambert M, Neish AC (1950) Rapid method for estimation of glycerol in fermentation solution. Can J Res 28:83–89

    Article  Google Scholar 

  18. Loray MA, De Figueroa LIC, Hofer M (1998) Effect of salt stress on sugar uptake in osmotolerant yeasts. Folia Microbiol (Praha) 43(2):204–206

    Article  CAS  Google Scholar 

  19. Papin JA, Price ND, Wiback SJ, Fell DA, Palsson BO (2003) Metabolic pathways in the post-genome era. Trends Biochem Sci 28(5):250–258

    Article  PubMed  CAS  Google Scholar 

  20. Poolman MG (2006) ScrumPy: metabolic modelling with Python. Syst Biol 153(5):375–378

    CAS  Google Scholar 

  21. Poolman MG, Fell DA, Raines CA (2003) Elementary modes analysis of photosynthate metabolism in the chloroplast stroma. Eur J Biochem 270(3):430–439

    Article  PubMed  CAS  Google Scholar 

  22. Reed RH, Chudek JA, Foster R, Gadd GM (1987) Osmotic significance of glycerol accumulation in exponentially growing yeasts. Appl Environ Microbiol 53(9):2119–2123

    PubMed  CAS  Google Scholar 

  23. Schilling CH, Letscher D, Palsson BO (2000) Theory for the systemic definition of metabolic pathways and their use in interpreting metabolic function from a pathway-oriented perspective. J Theor Biol 203(3):229–248

    Article  PubMed  CAS  Google Scholar 

  24. Schuster S, Dandekar T, Fell DA (1999) Detection of elementary flux modes in biochemical networks: a promising tool for pathway analysis and metabolic engineering. Trends Biotechnol 17(2):53–60

    Article  PubMed  CAS  Google Scholar 

  25. Schuster S, Fell DA, Dandekar T (2000) A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks. Nat Biotechnol 18(3):326–332

    Article  PubMed  CAS  Google Scholar 

  26. Schuster S, Hilgetag C (1994) On elementary flux modes in biochemical reaction systems at steady state. J Biol Syst 2:165–182

    Article  Google Scholar 

  27. Singh KK, Norton RS (1991) Metabolic changes induced during adaptation of Saccharomyces cerevisiae to a water stress. Arch Microbiol 156(1):38–42

    Article  PubMed  CAS  Google Scholar 

  28. Trinh CT, Carlson R, Wlaschin A, Srienc F (2006) Design, construction and performance of the most efficient biomass producing E. coli bacterium. Metab Eng 8(6):628–638

    Article  PubMed  CAS  Google Scholar 

  29. van Gulik WM, Heijnen JJ (1995) A metabolic network stoichiometry analysis of microbial growth and product formation. Biotechnol Bioeng 48(6):681–698

    Article  PubMed  Google Scholar 

  30. Vanrolleghem PA, de Jong-Gubbels P, van Gulik WM, Pronk JT, van Dijken JP, Heijnen S (1996) Validation of a metabolic network for Saccharomyces cerevisiae using mixed substrate studies. Biotechnol Prog 12(4):434–448

    Article  PubMed  CAS  Google Scholar 

  31. Wlaschin AP, Trinh CT, Carlson R, Srienc F (2006) The fractional contributions of elementary modes to the metabolism of Escherichia coli and their estimation from reaction entropies. Metabol Eng 8(4):338–352

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, Indian Institute of Technology, Bombay, Powai, Mumbai, 400076, India

    Jignesh H. Parmar, Sharad Bhartiya & K. V. Venkatesh

Authors
  1. Jignesh H. Parmar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharad Bhartiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. V. Venkatesh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. V. Venkatesh.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 47 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parmar, J.H., Bhartiya, S. & Venkatesh, K.V. Quantification of metabolism in Saccharomyces cerevisiae under hyperosmotic conditions using elementary mode analysis. J Ind Microbiol Biotechnol 39, 927–941 (2012). https://doi.org/10.1007/s10295-012-1090-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-012-1090-4

Keywords

Search

Navigation