Advertisement

Metabolomics pp 97-127 | Cite as

Reconstruction of dynamic network models from metabolite measurements

  • Matthias Reuss
  • Luciano Aguilera-Vázquez
  • Klaus Mauch
Chapter
Part of the Topics in Current Genetics book series (TCG, volume 18)

Abstract

One of the most ambitious and challenging goals of systems biology is the identification oftargets for reshaping biological systems based on quantitative predictions with the aid of mathematicalmodels. Whereas the potential and promise of biological systems modelling is substantial, severalobstacles are still encountered when addressing the issue of predictive design based on dynamic models.This is particularly because of the well known difficulties in assessing enzyme kinetics under in vivo conditions as a prerequisite for a sound quantitative analysis ofthe network via dynamic modelling. The article will describe developments and applications of toolsaimed at achieving sustained improvements within this important field. Our experience in using metabolitedata for reconstruction of dynamic models led to a dual approach. At the core of the modular conceptis the decomposition of the networks into manageable subunits. Furthermore, a new top down approachis presented for estimating kinetic parameters for the individual reactions in whole cell metabolicnetworks from time series data.

Keywords

Metabolic Network Intracellular Metabolite Metabolic Flux Analysis Metabolite Measurement Dynamic Network Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Aebersold R, Mann M (2003) Mass spectrometry-based proteomics. Nature 422:198–207 PubMedCrossRefGoogle Scholar
  2. 2.
    Aguilera-Vázquez L (2005) Modellgestützte Analyse der Dynamik des Speicherstoffwechsels in Saccharomyces cerevisiae. PhD Thesis, University Stuttgart, Shaker Verlag: Aachen Google Scholar
  3. 3.
    Alon U (2003) Biological networks: The tinkerer as an engineer. Science 26:1866–1867 CrossRefGoogle Scholar
  4. 4.
    Aon MA, Cortassa S (1997) Dynamic Biological Organization. Fundamentals as applied to cellular systems. London, Chapman & Hall CrossRefGoogle Scholar
  5. 5.
    Aragón JJ, Sánchez V (1985) Enzyme concentration affects the allosteric behaviour of yeast phosphofructokinase. Biochem Biophys Res Commun 131:849–855 PubMedCrossRefGoogle Scholar
  6. 6.
    Beullens M, Mbonyi K, Geerts L, Gladines D, Detremerie K, Jans AWH, Thevelein JM (1998) Studies on the mechanism of the glucose-induced cAMP signal in glycolysis and glucose repression mutants of the yeast Saccharomyces cerevisiae. Eur J Biochem 172:227–231 CrossRefGoogle Scholar
  7. 7.
    Buziol S, Bashir I, Baumeister A, Claassen W, Noisommit-Rizzi N, Mailinger W, Reuss M (2002) New bioreactor-coupled rapid stopped-flow sampling technique for measurements of metabolite dynamics on a subsecond time scale. Biotechnol Bioeng 80:632–636 PubMedCrossRefGoogle Scholar
  8. 8.
    Cannon JF, Tatchell K (1987) Characterization of Saccharomyces cerevisiae genes encoding subunits of cyclic AMP-dependent protein kinase. Mol Cell Biol 7:2653–2663 PubMedGoogle Scholar
  9. 9.
    Castrillo JI, Hayes A, Mohammed S, Gaskell SJ, Oliver SG (2003) An optimized protocol for metabolome analysis in yeast using direct infusion electrospray mass spectrometry. Phytochemistry 62:929–937 PubMedCrossRefGoogle Scholar
  10. 10.
    Chassagnole C, Noisommit-Rizzi N, Schmid JW, Mauch K, Reuss M (2002) Dynamic modelling of the central carbon metabolism of Escherichia coli. Biotechnol Bioeng 79:53–73 PubMedCrossRefGoogle Scholar
  11. 11.
    De Koning W, van Dam K (1992) A method for determination of changes of glycolytic metabolites in yeast on a subsecond time scale using extraction at neutral pH. Anal Biochem 204:118 -123 PubMedCrossRefGoogle Scholar
  12. 12.
    Ehrig R, Nowak U, Oeverdieck L, Deuflhard P (1999) Advanced extrapolation methods for large scale differential algebraic problems. In: Bunghartz HJ, Durst F, Zenger C (eds) High performance scientific and engineering computing (lecture notes in Computational Science and Engineering). Springer, Berlin 8:233–244 Google Scholar
  13. 13.
    Girvan M, Newman MEJ (2002) Community structure in social and biological networks. Proc Natl Acad Sci USA 99:7821–7826 PubMedCrossRefGoogle Scholar
  14. 14.
    Gonzales B, Francois J, Renaud M (1997) A rapid and reliable method for metabolite extraction in yeast using boiling buffered ethanol. Yeast 13:1347–1356 CrossRefGoogle Scholar
  15. 15.
    Guimera R, Amaral LAN (2005) Functional cartography of complex metabolic networks. Nature 433:895–900 PubMedCrossRefGoogle Scholar
  16. 16.
    Hixson CS, Krebs EG (1980) Characterization of a cyclic AMP-binding protein from baker's yeast. J Biol Chem 255:2137–2145 PubMedGoogle Scholar
  17. 17.
    Hofmann E, Kopperschläger G (1982) Phosphofructokinase from yeast. Meth Enzymol 90:49–60 PubMedCrossRefGoogle Scholar
  18. 18.
    Holme P, Huss M, Jeong H (2003) Subnetwork hierarchies of biochemical pathways. Bioinformatics 19:532–538 PubMedCrossRefGoogle Scholar
  19. 19.
    Huss M, Holme P (2006) Currency and commodity metabolites: Their identification and relation to the modularity of metabolic networks. Quantitative Biology q-bio. MN/0603038, arXiv.org Google Scholar
  20. 20.
    Janssens V, Goris J (2001) Protein phophatase 2A: a highly regulated family of serine/threonine phophatases implicated in cell growth and signalling. Biochem J 353:417–439 PubMedCrossRefGoogle Scholar
  21. 21.
    Karp PD, Arnaud M, Collado-Vides J, Ingraham J, Paulsen I, Saier M (2004) The E. coli ecocyc data base: No longer just a metabolic pathway database. ASM News 70:25–30 Google Scholar
  22. 22.
    Kopperschläger G (1999) personal communication Google Scholar
  23. 23.
    Kremling A, Stelling J, Bettenbrock S, Fischer S, Gilles ED (2005) Metabolic networks: biology meets engineering sciences. In: Alberghina L, Westerhoff HV (eds) Topics in Current Genetics: Systems Biology- Definitions and Perspectives. Springer, Berlin 13:215–234 Google Scholar
  24. 24.
    Mailinger W, Baumeister A, Reuss M, Rizzi M (1998) Rapid and highly automated determination of adenine and pyridine nucleotides in extracts of Saccharomyces cerevisiae using a micro robotic sample preparation-HPLC system. J Biotechnol 63:155–166 PubMedCrossRefGoogle Scholar
  25. 25.
    Masegho MR, van Gulik WM, Vinke JL, Visser D, Heijnen JJ (2006) In vivo kinetics with rapid perturbation experiments in Saccharomyces cerevisiae using a second-generation BioScope. Metabol Eng 8:370–383 CrossRefGoogle Scholar
  26. 26.
    Matsumoto K, Uno I, Tohe A, Ishikawa T, Oshiuma Y (1982a) Cyclic AMP may not be involved in catabolic repression in Saccharomyces cerevisiae: evidence from mutants capable of utilising it as an adenine source. J Bacteriol 150:277–285 PubMedGoogle Scholar
  27. 27.
    Matsumoto K, Uno I, Oshima Y, Ishikawa T (1982b) Isolation and characterisation of yeast mutant deficient in adenylate cyclase and cAMP-dependent protein kinase. Proc Nat Acad Sci USA 79:2355–2359 PubMedCrossRefGoogle Scholar
  28. 28.
    Mauch K, Vaseghi S, Reuss M (2000) Quantitative analysis of metabolic and signalling pathways in Saccharomyces cerevisiae. In: Schügerl K, Bellgardt KH (eds) Bioreaction Engineering. Springer, Berlin 435–477 Google Scholar
  29. 29.
    Moritz B, Meyer HE (2003) Approaches for the quantification of protein concentration ratios. Proteomics 3:2208–2220 PubMedCrossRefGoogle Scholar
  30. 30.
    Müller D (2006) Model-assisted analysis of cyclic AMP signal transduction in Saccharomyces cerevisiae – cAMP as dynamic coordinator of energy metabolism and cell cycle progression. PhD Thesis, University Stuttgart, Shaker Verlag, Aachen Google Scholar
  31. 31.
    Müller D, Aguilera-Vázquez L, Barl T, Diaz-Cuervo H, Guerrero-Martin E, Marquetand JO, Murugan PK, Niebel A, Reuss M (2005) Integration of cyclic AMP signaling and metabolism in a single-cell model of Saccharomyces cerevisiae. FOSBE 2005, Santa Barabara, Proceedings, CACHE: 249–254 Google Scholar
  32. 32.
    Murray W (1999) From molecular to modular cell biology. Nature 402:C47–C52 PubMedCrossRefGoogle Scholar
  33. 33.
    Newman MEJ, Girvan M (2004) Finding and evaluating community structure in networks. Phys Rev E69:026113 Google Scholar
  34. 34.
    Radicchi F, Castellano C, Cecconi F, Loreto V, Parisi D (2004) Defining and identifying communities in networks. Proc Natl Acad Sci USA 101:2658–2663 PubMedCrossRefGoogle Scholar
  35. 35.
    Ravasz E, Somera AL, Mongru DA, Oltvai ZN, Barabasi AL (2002) Hierarchical organisation of modularity in metabolic networks. Science 297:1551–1555 PubMedCrossRefGoogle Scholar
  36. 36.
    Reuss M (1991) Structured modeling of Bioreactors. Ann NY Acad Sci 646:284–299 CrossRefGoogle Scholar
  37. 37.
    Reuter R, Eschrich K, Schellenberger W, Hofman E (1979) Kinetic modelling of yeast phosphofructokinase. Acta Biol Med Germ 38:1067–1079 PubMedGoogle Scholar
  38. 38.
    Rizzi M, Theobald U, Querfurth E, Rohrhirsch T, Baltes M, Reuss M (1996) In vivo investigations of glucose transport in Saccharomyces cerevisiae. Biotechnol Bioeng 52:316–327 Google Scholar
  39. 39.
    Rizzi M, Baltes M, Theobald U, Reuss M (1997) In vivo analysis of metabolic dynamics in Saccharomyces cerevisiae: II Mathematical model. Biotechnol Bioeng 55:592–608 PubMedCrossRefGoogle Scholar
  40. 40.
    Schaefer U, Boos W, Takors R, Weuster-Botz D (1999) Automated sampling device for monitoring intracellular metabolite dynamics. Anal Biochem 270:88–96 PubMedCrossRefGoogle Scholar
  41. 41.
    Schaub J, Schiesling C, Reuss M, Dauner M (2006) Integrated sampling procedure for metabolome analysis. Biotechnol Progr 22:1434–1442 CrossRefGoogle Scholar
  42. 42.
    Schmid JW, Mauch K, Reuss M, Gilles ED, Kremling A (2004) Metabolic design based on coupled gene expression-metabolic network model of tryptophan production in Escherichia coli. Metabol Eng 6:364–377 CrossRefGoogle Scholar
  43. 43.
    Serrano R, Gancedo JM, Gancedo C (1973) Assay of yeast enzymes in situ. Eur J Biochem 34:479–482 PubMedCrossRefGoogle Scholar
  44. 44.
    Schmalzried S, Jenne M, Mauch K, Reuss M (2003) Integration of physiology and fluid dynamics. Adv Biochem Eng 80:19–68 Google Scholar
  45. 45.
    Snoep JL, Bruggeman F, Olivier BG, Westerhoff HV (2006) Towards building the silicon cell: a modular approach. Biosystems 83:207–216 PubMedCrossRefGoogle Scholar
  46. 46.
    Srere PA (1967) Enzyme concentrations in tissues. Science 158:936–937 PubMedCrossRefGoogle Scholar
  47. 47.
    Streichert F, Ulmer H, Zell A (2005) Java Eva: A Java based framework for evolutionary algorithms. www-ra.informatik.uni-tuebingen.de/software/javaeva Google Scholar
  48. 48.
    Teusink B, Passarge J, Reijenga CA, Esgalhado E, van der Weijden CC, Schepper M, Walsh MC, Bakker BM, van Dam K, Westerhoff HV, Snoep JL (2000) Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry. Eur J Biochem 267:5313–5329 PubMedCrossRefGoogle Scholar
  49. 49.
    Theobald U, Mailinger W, Reuss M, Rizzi M (1993) In vivo analysis of glucose-induced fast changes in yeast adenine nucleotide pool applying a rapid sampling technique. Anal Biochem 214:31–37 PubMedCrossRefGoogle Scholar
  50. 50.
    Theobald U, Mailinger W, Rizzi M (1994) Use of HgCl2 to investigate dynamic phenomena in yeast cytoplasm. Biotechnol Techniques 8:723–728 CrossRefGoogle Scholar
  51. 51.
    Theobald U, Mailinger W, Baltes M, Rizzi M, Reuss M (1997) In vivo analysis of metabolic dynamics in Saccharomyces cerevisiae: I. Experimental observations. Biotechnol Bioeng 55:305–316 PubMedCrossRefGoogle Scholar
  52. 52.
    Thevelein JM, de Winde JH (1999) Novel sensing mechanisms and targets for the cAMP-protein kinase A pathway in the yeast Saccharomyces cerevisiae. Mol Microbiol 33:904–918 PubMedCrossRefGoogle Scholar
  53. 53.
    Toda A, Cameron S, Sass P, Zoller M, Wigler M (1987a) Three different genes in Saccharomyces cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase. Cell 50:277–287 PubMedCrossRefGoogle Scholar
  54. 54.
    Toda A, Cameron S, Sass P, Zoller M, Scott JD, McBullen B, Hurwitz M, Krebs EG, Wigler M (1987b) Cloning and characterization of BCY1, a locus encoding a regulatory subunit of cyclic AMP-dependent protein kinase in Saccharomyces cerevisiae. Mol Cell Biol 7:1371–1377 PubMedGoogle Scholar
  55. 55.
    Van Schaftingen E, Lederer B, Bartons R, Hers HG (1982) A kinetic study of pyrophosphate: Fructose-6-phosphate phosphotransferase from potato tubers. Eur J Biochem 129:191–195 PubMedCrossRefGoogle Scholar
  56. 56.
    Vaseghi S, Baumeister A, Rizzi M, Reuss M (1999) In vivo dynamics of the pentose phosphate pathway in Saccharomyces cerevisiae. Metabol Eng 1:128–140 CrossRefGoogle Scholar
  57. 57.
    Vaseghi S (2000) Modellgestützte Analyse der Dynamik des Phosphofructokinas-Systems in Saccharomyces cerevisiae. PhD Thesis, University Stuttgart Google Scholar
  58. 58.
    Vaseghi S, Macherhammer F, Zibek S, Reuss M (2001) Signal transduction dynamics of the protein kinase A/Phosphofructokinase-2-system in Saccharomyces cerevisiae. Metabol Eng 3:163–172 CrossRefGoogle Scholar
  59. 59.
    Visser D, van Zuylen GA, van Dam JC, Oudshoorn A, Eman MR, Ras C, van Gulik WM, Frank J, van Dedem GWK, Heijnen JJ (2002) Rapid sampling for analysis of in vivo kinetics using the BioScope: a system for continuous-pulse experiments. Biotechnol Bioeng 79:674–681 PubMedCrossRefGoogle Scholar
  60. 60.
    Visser D, Heijnen JJ (2003) Dynamic simulation and metabolic redesign of a branched pathway using linlog kinetics. Metabol Eng 5:164–176 CrossRefGoogle Scholar
  61. 61.
    Visser D, Schmid J, Mauch K, Reuss M, Heijnen JJ (2004) Optimal re-design of primary metabolism in Escherichia coli using linlog kinetics. Metabol Eng 6:378–390 CrossRefGoogle Scholar
  62. 62.
    Weibel KE, Mor JR, Fiechter A (1974) Rapid sampling of yeast cells and automated assays of adenylate, citrate, pyruvate and glucose-6-phosphate pools. Anal Biochem 58:208–216 PubMedCrossRefGoogle Scholar
  63. 63.
    Weuster-Botz D, de Graaf AA (1996) Reaction engineering methods to study intracellular metabolite concentrations. Adv Biochem Eng 54:75–108 Google Scholar
  64. 64.
    Wingender-Drissen R (1983) Yeast cyclic AMP-dependent protein kinase. FEBS Lett 163:28–32 PubMedCrossRefGoogle Scholar
  65. 65.
    Wu L, Wang W, van Winden WQA, van Gulik WM, Heijnen JJ (2004) A new framework for the estimation of control parameters in metabolic pathways using lin-log kinetics. Eur J Biochem 271:3348–3359 PubMedCrossRefGoogle Scholar
  66. 66.
    Wu L, Masegho MR, Proell AM, Vinke JL, Ras C, van Dam JC, van Winden WA, van Gulik WM, Heijnen JJ (2006) In vivo kinetics of primary metabolism in S. cerevisiae studied through prolonged chemostate cultivation. Metabol Eng 8:160–171 CrossRefGoogle Scholar
  67. 67.
    Yamashoji S, Hess B (1984) Activation of yeast 6-phosphofructo-2-kinase by protein kinase and phosphate. FEBS Lett 178:253–256 PubMedCrossRefGoogle Scholar
  68. 68.
    Zhao Y, Boguslawski G, Zitomer RS, DePaoli-Roach AA (1997) Saccharomyces cerevisiae homologs of mammalian B and B' subunits of protein phosphatase 2A direct the enzyme to distinct cellular functions. J Biol Chem 272:8256–8262 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • Matthias Reuss
    • 1
  • Luciano Aguilera-Vázquez
    • 2
  • Klaus Mauch
    • 3
  1. 1.Institute of Biochemical Engineering and Centre of Systems BiologyUniversity StuttgartStuttgartGermany
  2. 2.Depto.de BiotecnologíaUniversidad Politécnica de PachucaMunicipio de Zenpoala, HgoMexico
  3. 3.Insilico Biotechnology AGStuttgartGermany

Personalised recommendations