13C-based metabolic flux analysis

Nature Protocols

Volumn 4, Issue 6, 2009, Pages 878-892

  Zamboni, Nicola ^a   Fendt, Sarah Maria ^a   Rühl, Martin ^a   Sauer, Uwe ^a  

^a ETH ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; CARBON 13; GLUCOSE;

AMINO ACID ANALYSIS; ANALYTIC METHOD; ARTICLE; BACTERIAL METABOLISM; BACTERIUM CULTURE; CELL METABOLISM; CONTINUOUS CULTURE; ESCHERICHIA COLI; GLUCOSE METABOLISM; ISOTOPE ANALYSIS; ISOTOPE LABELING; ISOTOPE TRACING; MASS FRAGMENTOGRAPHY; MICROBIAL GROWTH; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN STABILITY; TRANSPORT KINETICS;

AMINO ACIDS; CARBON ISOTOPES; ESCHERICHIA COLI; ESCHERICHIA COLI PROTEINS; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; GLUCOSE; METABOLIC NETWORKS AND PATHWAYS; METABOLOMICS; MODELS, BIOLOGICAL;

ESCHERICHIA COLI;

EID: 66749182798     PISSN: 17542189     EISSN: 17502799     Source Type: Journal    
DOI: 10.1038/nprot.2009.58     Document Type: Article

References (76)

1. Ishii, N. et al. Multiple high-throughput analyses monitor the response of E. coli to perturbations. Science 316, 593-597 (2007).
2. 13C-based flux analysis. Mol. Syst. Biol. 2, 62 (2006).
3. Hellerstein, M.K. In vivo measurement of fluxes through metabolic pathways: The missing link in functional genomics and pharmaceutical research. Annu. Rev. Nutr. 23, 379-402 (2003).
4. Stephanopoulos, G. Metabolic fluxes and metabolic engineering. Metab. Eng. 1, 1-11 (1999).
5. Varma, A. & Palsson, B.O. Metabolic flux balancing: Basic concepts, scientific, and practical use. Bio/Technol. 12, 994-998 (1994).
6. 13C metabolic flux analysis. Metab. Eng. 3, 195-206 (2001).
7. 13C-NMR, MS and metabolic flux balancing in biotechnology research. Q. Rev. Biophys. 31, 41-106 (1998).
8. 13C-experiments and gas chromatography-mass spectrometry data: Protocol and principles. Methods Mol. Biol. 358, 177-197 (2007).
9. Sauer, U. High-throughput phenomics: Experimental methods for mapping fluxomes. Curr. Opin. Biotechnol. 15, 58-63 (2004).
10. 13C metabolic flux analysis. Metab. Eng. 3, 265-283 (2001).
11. Fischer, E. & Sauer, U. Metabolic flux profiling of Escherichia coli mutants in central carbon metabolism using GC-MS. Eur. J. Biochem. 270, 880-891 (2003).
12. 13C-glucose experiments. BMC Bioinformatics 6, 209 (2005).
13. Marx, A., de Graaf, A.A., Wiechert, W., Eggeling, L. & Sahm, H. Determination of the fluxes in the central metabolism of Corynebacterium glutamicum by nuclear magnetic resonance spectroscopy combined with metabolite balancing. Biotech. Bioeng. 49, 111-129 (1996).
14. 13C constraints. Anal. Biochem. 325, 308-316 (2004).
15. Emmerling, M. et al. Metabolic flux responses to pyruvate kinase knockout in Escherichia coli. J. Bacteriol. 184, 152-164 (2002).
16. Dauner, M. & Sauer, U. GC-MS analysis of amino acids rapidly provides rich information for isotopomer balancing. Biotechnol. Prog. 16 642-649 (2000).
17. 13C labeling experiments. J. Biotechnol. 129, 249-267 (2007).
18. 13C-labeled primary metabolites. FEMS Yeast Res. 5, 559-568 (2005).
19. Yuan, J., Fowler, W.U., Kimball, E., Lu, W. & Rabinowitz, J.D. Kinetic flux profiling of nitrogen assimilation in Escherichia coli. Nat. Chem. Biol. 2, 529-530 (2006).
20. 13C labeling data. Biotechnol. Bioeng. 99, 1170-1185 (2008).
21. Hua, Q., Yang, C., Baba, T., Mori, H. & Shimizu, K. Responses of the central metabolism in Escherichia coli to phosphoglucose isomerase and glucose-6-phosphate dehydrogenase knockouts. J. Bacteriol. 185, 7053-7067 (2003).
22. Fischer, E. & Sauer, U. Large-scale in vivo flux analysis shows rigidity and suboptimal performance of Bacillus subtilis metabolism. Nat. Genet. 37, 636-640 (2005).
23. 13C-labeling experiments. Eur. J. Biochem. 269, 2795-2800 (2002).
24. Wittmann, C., Kiefer, P. & Zelder, O. Metabolic fluxes in Corynebacterium glutamicum during lysine production with sucrose as carbon source. Appl. Environ. Microbiol. 70, 7277-7287 (2004).
25. Hellerstein, M.K. New stable isotope-mass spectrometric techniques for measuring fluxes through intact metabolic pathways in mammalian systems: introduction of moving pictures into functional genomics and biochemical phenotyping. Metab. Eng. 6, 85-100 (2004).
26. Schwender, J. Metabolic flux analysis as a tool in metabolic engineering of plants. Curr. Opin. Biotechnol. 19, 131-137 (2008).
27. Wittmann, C. Metabolic flux analysis using mass spectrometry. Adv. Biochem. Eng. Biotechnol. 74, 39-64 (2002).
28. Gunnarsson, N., Mortensen, U.H., Sosio, M. & Nielsen, J. Identification of the Entner-Doudoroff pathway in an antibiotic-producing actinomycete species. Mol. Microbiol. 52, 895-902 (2004).
29. Fischer, E. & Sauer, U. A novel metabolic cycle catalyzes glucose oxidation and anaplerosis in hungry Escherichia coli. J. Biol. Chem. 278, 46446-46451 (2003).
30. 13C-flux analysis reveals mechanistic principles of metabolic network robustness to null mutations in yeast. Genome. Biol. 6, R49 (2005).
31. Schütz, R., Küpfer, L. & Sauer, U. Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli. Mol. Syst. Biol. 3, 119 (2007).
32. Feist, A.M. & Palsson, B.O. The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli. Nat. Biotechnol. 26, 659-667 (2008).
33. 13C-labeling of proteinogenic amino acids. An efficient analytical tool to investigate intermediary metabolism. Eur. J. Biochem. 232, 433-448 (1995).
34. Möllney, M., Wiechert, W., Kownatzki, D. & de Graaf, A.A. Bidirectional reaction steps in metabolic networks: IV. Optimal design of isotopomer labeling experiments. Biotechnol. Bioeng. 66, 86-103 (1999).
35. Wiechert, W., Siefke, C., de Graaf, A.A. & Marx, A. Bidirectional reaction steps in metabolic networks: II. Flux estimation and statistical analysis. Biotechnol. Bioeng. 55, 118-135 (1997).
36. Antoniewicz, M.R., Kelleher, J.K. & Stephanopoulos, G. Elementary metabolite units (EMU): A novel framework for modeling isotopic distributions. Metab. Eng. 9, 68-86 (2007).
37. 1H] COSY NMR data. Biotechnol. Bioeng. 80, 731-745 (2002).
38. Rantanen, A. et al. An analytic and systematic framework for estimating metabolic flux ratios from 13C tracer experiments. BMC Bioinformatics 9, 266 (2008).
39. Zamboni, N. et al. Transient expression and flux changes during a shift from high to low riboflavin production in continuous cultures of Bacillus subtilis. Biotechnol. Bioeng. 89, 219-232 (2005).
40. Schaub, J., Schiesling, C., Reuss, M. & Dauner, M. Integrated sampling procedure for metabolome analysis. Biotechnol. Prog. 22, 1434-1442 (2006).
41. Antoniewicz, M.R. et al. Metabolic flux analysis in a nonstationary system: Fedbatch fermentation of a high yielding strain of E. coli producing 1,3-propanediol. Metab. Eng. 9, 277-292 (2007).
42. Monod, J. Récherches sur la croissance des cultures bactériennnes (Hermann et Compagnie Ed, Paris, 1942).
43. 13C-labeled gluconate tracing as a direct and accurate method for determining the pentose phosphate pathway split ratio in Penicillium chrysogenum. Appl. Environ. Microbiol. 72 4743-4754 (2006).
44. Petersen, S. et al. In vivo quantification of parallel and bidirectional fluxes in the anaplerosis of Corynebacterium glutamicum. J. Biol. Chem. 275, 35932-35941 (2000).
45. Stryer, L. Biochemistry 4th edn. 483-491 (Freeman and Company, New York, 1995).
46. Dauner, M. et al. Intracellular carbon fluxes in riboflavin-producing Bacillus subtilis during growth on two-carbon substrate mixtures. Appl. Environ. Microbiol. 68, 1760-1771 (2002).
47. Blank, L.M., Lehmbeck, F. & Sauer, U. Metabolic-flux and network analysis in fourteen hemiascomycetous yeasts. FEMS Yeast Res. 5 545-558 (2005).
48. 13C constraints. Anal. Biochem. 325, 308-316 (2004).
49. Kleijn, R.J. et al. Metabolic flux analysis of a glycerol-overproducing Saccharomyces cerevisiae strain based on GC-MS, LC-MS and NMR-derived C-13-labelling data. FEMS Yeast Res. 7, 216-231 (2007).
50. Kummel, A., Panke, S. & Heinemann, M. Systematic assignment of thermodynamic constraints in metabolic network models. BMC Bioinformatics 7, 512 (2006).
51. Herrgard, M.J. et al. A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology. Nat. Biotechnol. 26, 1155-1160 (2008).
52. Oh, Y.K., Palsson, B.O., Park, S.M., Schilling, C.H. & Mahadevan, R. Genome-scale reconstruction of metabolic network in Bacillus subtilis based on high-throughput phenotyping and gene essentiality data. J. Biol. Chem. 282, 28791-28799 (2007).
53. Feist, A.M. et al. A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information. Mol. Syst. Biol. 3, 121 (2007).
54. Schilling, C.H. et al. Genome-scale metabolic model of Helicobacter pylori 26695. J. Bacteriol. 184, 4582-4593 (2002).
55. Oliveira, A.P., Nielsen, J. & Forster, J. Modeling Lactococcus lactis using a genomescale flux model. BMC Microbiol. 5, 39 (2005).
56. 13C-labeled glucose and gas chromatography-mass spectrometry. Metab. Eng. 6 340-351 (2004).
57. Fuhrer, T., Fischer, E. & Sauer, U. Experimental identification and quantification of glucose metabolism in seven bacterial species. J. Bacteriol. 187, 1581-1590 (2005).
58. Schmidt, K., Carlsen, M., Nielsen, J. & Villadsen, J. Modeling isotopomer distributions in biochemical networks using isotopomer mapping matrices. Biotechnol. Bioeng. 55, 831-840 (1997).
59. Arita, M. In silico atomic tracing by substrate-product relationships in Escherichia coli intermediary metabolism. Genome Res. 13, 2455-2466 (2003).
60. Pitkänen, E., Åkerlund, A., Rantanen, A., Jouhten, P. & Ukkonen, E. ReMatch: A web-based tool to construct, store and share stoichiometric metabolic models with carbon maps for metabolic flux analysis. J. Integr. Bioinform. 5, 102 (2008).
61. Dauner, M., Bailey, J.E. & Sauer, U. Metabolic flux analysis with a comprehensive isotopomer model in Bacillus subtilis. Biotechnol. Bioeng. 76, 144-156 (2001).
62. Pramanik, J. & Keasling, J.D. Effect of Escherichia coli biomass composition on central metabolic fluxes predicted by a stoichiometric model. Biotechnol. Bioeng. 60, 230-238 (1998).
63. Guy, R.D., Fogel, M.L. & Berry, J.A. Photosynthetic fractionation of the stable isotopes of oxygen and carbon. Plant Physiol. 101, 37-47 (1993).
64. Srere, P.A. Citric acid cycle redux. Trends Biochem. Sci. 15 411-412 (1990).
65. Antoniewicz, M.R., Kelleher, J.K. & Stephanopoulos, G. Accurate assessment of amino acid mass isotopomer distributions for metabolic flux analysis. Anal. Chem. 79, 7554-7559 (2007).
66. Zamboni, N. in Topics in Current Genetics (eds. J. Nielsen & M. Jewett) (Springer, Berlin, 2007).
67. Isermann, N. & Wiechert, W. Metabolic isotopomer labeling systems. Part II: Structural flux identifiability analysis. Math. Biosci. 183 175-214 (2003).
68. Rantanen, A., Mielikainen, T., Rousu, J., Maaheimo, H. & Ukkonen, E. Planning optimal measurements of isotopomer distributions for estimation of metabolic fluxes. Bioinformatics 22, 1198-1206 (2006).
69. Sambrook, T. & Russell, D.W. in Molecular Cloning: A Laboratory Manual Vol 3, A2.2 (Cold Spring Harbor Press, Cold Spring Harbor, NY, 2001).
70. Bailey, J.E. & Ollis, D.F. in Biochemical Engineering Fundamentals 2nd edn. 373-456 (McGraw-Hill, Singapore, 1986).
71. Wahl, S.A., Dauner, M. & Wiechert, W. New tools for mass isotopomer data evaluation in (13)C flux analysis: Mass isotope correction, data consistency checking, and precursor relationships. Biotechnol. Bioeng. 85, 259-268 (2004).
72. Pázman, A. Nonlinear Statistical Models (Kluwer Academic Publishing, New York, 1993).
73. Gottschalk, G. Bacterial Metabolism 2nd edn. 185 (Springer-Verlag, New York, 1986).
74. Fong, S.S., Nanchen, A., Palsson, B.O. & Sauer, U. Latent pathway activation and increased pathway capacity enable Escherichia coli adaptation to loss of key metabolic enzymes. J. Biol. Chem. 281 8024-8033 (2006).
75. Wiechert, W. & de Graaf, A.A. Bidirectional reaction steps in metabolic networks: I. Modeling and simulation of carbon isotope labeling experiments. Biotechnol. Bioeng. 55, 101-117 (1997).
76. Wiechert, W., Mollney, M., Isermann, N., Wurzel, M. & de Graaf, A.A. Bidirectional reaction steps in metabolic networks: III. Explicit solution and analysis of isotopomer labeling systems. Biotechnol. Bioeng. 66, 69-85 (1999).