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E. coli metabolomics: capturing the complexity of a “simple” model

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Metabolomics

Part of the book series: Topics in Current Genetics ((TCG,volume 18))

Abstract

As the workhorse of early studies on metabolism, the metabolic pathways of E.coli are arguably the best characterized. The richness of information available aboutits pathways is broader than for any other model. However, in spite of decades of descriptive work,only recently can a significant number of E. coli metabolicnetwork constituents be analyzed simultaneously. The advent of metabolomic methods that allow tocapture qualitative as well as quantitative information about the intracellular and extracellularmetabolite profiles is starting to shed light on the remaining complexity of this simpler model. Herewe describe important findings about the physiology of E. coliresulting from emerging metabolomic studies. While a vast number of intracellular metabolitesin E. coli still remain to be characterized, the information obtainedfrom those studies can provide an unprecedented amount of information about metabolic pathways includingtheir functional elucidation, enzyme activity, metabolic fluxes, network robustness, or even the discoveryof completely novel reactions or pathways. These results are also being used to populate rich databasesand to develop computational models of E. coli metabolism thathave already proven effective to predict cellular states and will shed light on complex and untilnow still elusive regulatory principles.

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References

  1. Allen J, Davey HM, Broadhurst D, Heald JK, Rowland JJ, Oliver SG, Kell DB (2003) High-throughput classification of yeast mutants for functional genomics using metabolic footprinting. Nat Biotechnol 6:692–696

    Google Scholar 

  2. Almaas E, Kovacs B, Vicsek T, Oltvai ZN, Barabasi AL (2004) Global organization of metabolic fluxes in the bacterium Escherichia coli. Nature 427:839–843

    PubMed  CAS  Google Scholar 

  3. Arakawa K, Kono N, Yamada Y, Mori H, Tomita M (2005) KEGG-based pathway visualization tool for complex omics data. In Silico Biol 5:419–423

    PubMed  CAS  Google Scholar 

  4. Arakawa K, Yamada Y, Shinoda K, Nakayama Y, Tomita M (2006) GEM System: automatic prototyping of cell-wide metabolic pathway models from genomes. BMC Bioinformatics 7:168

    PubMed  Google Scholar 

  5. Arita M (2003) In silico atomic tracing by substrate-product relationships in Escherichia coli intermediary metabolism. Genome Res 13:2455–2466

    PubMed  CAS  Google Scholar 

  6. Arita M (2004) The metabolic world of Escherichia coli is not small. Proc Natl Acad Sci USA 101:1543–1547

    PubMed  CAS  Google Scholar 

  7. Arita M, Robert M, Tomita M (2005) All systems go: launching cell simulation fueled by integrated experimental biology data. Curr Opin Biotechnol 16:344–349

    PubMed  CAS  Google Scholar 

  8. Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006) Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol Syst Biol 2:2006 0008

    Google Scholar 

  9. Bajad SU, Lu W, Kimball EH, Yuan J, Peterson C, Rabinowitz JD (2006) Separation and quantitation of water soluble cellular metabolites by hydrophilic interaction chromatography-tandem mass spectrometry. J Chromatogr A 1125:76–88

    PubMed  CAS  Google Scholar 

  10. Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S (2004) Bacterial persistence as a phenotypic switch. Science 305:1622–1625

    PubMed  CAS  Google Scholar 

  11. Baran R, Kochi H, Saito N, Suematsu M, Soga T, Nishioka T, Robert M, Tomita M (2006) MathDAMP: a package for differential analysis of metabolite profiles. BMC Bioinformatics 7:530

    PubMed  Google Scholar 

  12. Becker D, Selbach M, Rollenhagen C, Ballmaier M, Meyer TF, Mann M, Bumann D (2006) Robust Salmonella metabolism limits possibilities for new antimicrobials. Nature 440:303–307

    PubMed  CAS  Google Scholar 

  13. Berry A (1996) Improving production of aromatic compounds in Escherichia coli by metabolic engineering. Trends Biotechnol 14:250–256

    PubMed  CAS  Google Scholar 

  14. Bhattacharya M, Fuhrman L, Ingram A, Nickerson KW, Conway T (1995) Single-run separation and detection of multiple metabolic intermediates by anion-exchange high-performance liquid chromatography and application to cell pool extracts prepared from Escherichia coli. Anal Biochem 232:98–106

    PubMed  CAS  Google Scholar 

  15. Bino RJ, Hall RD, Fiehn O, Kopka J, Saito K, Draper J, Nikolau BJ, Mendes P, Roessner-Tunali U, Beale MH, Trethewey RN, Lange BM, Wurtele ES, Sumner LW (2004) Potential of metabolomics as a functional genomics tool. Trends Plant Sci 9:418–425

    PubMed  CAS  Google Scholar 

  16. Birkemeyer C, Luedemann A, Wagner C, Erban A, Kopka J (2005) Metabolome analysis: the potential of in vivo labeling with stable isotopes for metabolite profiling. Trends Biotechnol 23:28–33

    PubMed  CAS  Google Scholar 

  17. Bochner BR (2003) New technologies to assess genotype-phenotype relationships. Nat Rev Genet 4:309–314

    PubMed  CAS  Google Scholar 

  18. Bochner BR, Gadzinski P, Panomitros E (2001) Phenotype microarrays for high-throughput phenotypic testing and assay of gene function. Genome Res 11:1246–1255

    PubMed  CAS  Google Scholar 

  19. Brauer MJ, Yuan J, Bennett BD, Lu W, Kimball E, Botstein D, Rabinowitz JD (2006) Conservation of the metabolomic response to starvation across two divergent microbes. PNAS 103:19302–19307

    PubMed  CAS  Google Scholar 

  20. Buchholz A, Hurlebaus J, Wandrey C, Takors R (2002) Metabolomics: quantification of intracellular metabolite dynamics. Biomol Eng 19:5–15

    PubMed  CAS  Google Scholar 

  21. Buchholz A, Takors R, Wandrey C (2001) Quantification of intracellular metabolites in Escherichia coli K12 using liquid chromatographic-electrospray ionization tandem mass spectrometric techniques. Anal Biochem 295:129–137

    PubMed  CAS  Google Scholar 

  22. Burgard AP, Vaidyaraman S, Maranas CD (2001) Minimal reaction sets for Escherichia coli metabolism under different growth requirements and uptake environments. Biotechnol Prog 17:791–797

    PubMed  CAS  Google Scholar 

  23. 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

    PubMed  CAS  Google Scholar 

  24. Chang DE, Jung HC, Rhee JS, Pan JG (1999) Homofermentative production of D- or L-lactate in metabolically engineered Escherichia coli RR1. Appl Environ Microbiol 65:1384–1389

    PubMed  CAS  Google Scholar 

  25. Chassagnole C, Noisommit-Rizzi N, Schmid JW, Mauch K, Reuss M (2002) Dynamic modeling of the central carbon metabolism of Escherichia coli. Biotechnol Bioeng 79:53–73

    PubMed  CAS  Google Scholar 

  26. Chen H, Pan Z, Talaty N, Raftery D, Cooks RG (2006) Combining desorption electrospray ionization mass spectrometry and nuclear magnetic resonance for differential metabolomics without sample preparation. Rapid Commun Mass Spectrom 20:1577–1584

    PubMed  CAS  Google Scholar 

  27. Chen L, Vitkup D (2006) Predicting genes for orphan metabolic activities using phylogenetic profiles. Genome Biol 7:R17

    PubMed  Google Scholar 

  28. Clayton TA, Lindon JC, Cloarec O, Antti H, Charuel C, Hanton G, Provost JP, Le Net JL, Baker D, Walley RJ, Everett JR, Nicholson JK (2006) Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature 440:1073–1077

    PubMed  CAS  Google Scholar 

  29. Cooks RG, Ouyang Z, Takats Z, Wiseman JM (2006) Detection Technologies. Ambient mass spectrometry. Science 311:1566–1570

    PubMed  CAS  Google Scholar 

  30. Coulier L, Bas R, Jespersen S, Verheij E, van der Werf MJ, Hankemeier T (2006) Simultaneous quantitative analysis of metabolites using ion-pair liquid chromatography-electrospray ionization mass spectrometry. Anal Chem 78:6573–6582

    PubMed  CAS  Google Scholar 

  31. Covert MW, Knight EM, Reed JL, Herrgard MJ, Palsson BO (2004) Integrating high-throughput and computational data elucidates bacterial networks. Nature 429:92–96

    PubMed  CAS  Google Scholar 

  32. Covert MW, Palsson BO (2002) Transcriptional regulation in constraints-based metabolic models of Escherichia coli. J Biol Chem 277:28058–28064

    PubMed  CAS  Google Scholar 

  33. Covert MW, Palsson BO (2003) Constraints-based models: regulation of gene expression reduces the steady-state solution space. J Theor Biol 221:309–325

    PubMed  CAS  Google Scholar 

  34. Crockford DJ, Holmes E, Lindon JC, Plumb RS, Zirah S, Bruce SJ, Rainville P, Stumpf CL, Nicholson JK (2006) Statistical heterospectroscopy, an approach to the integrated analysis of NMR and UPLC-MS data sets: application in metabonomic toxicology studies. Anal Chem 78:363–371

    PubMed  CAS  Google Scholar 

  35. de Koning W, van Dam K (1992) A method for the determination of changes of glycolytic metabolites in yeast on a subsecond time scale using extraction at neutral pH. Anal Biochem 204:118–123

    PubMed  Google Scholar 

  36. Di Carlo D, Aghdam N, Lee LP (2006) Single-cell enzyme concentrations, kinetics, and inhibition analysis using high-density hydrodynamic cell isolation arrays. Anal Chem 78:4925–4930

    PubMed  Google Scholar 

  37. Dovichi NJ, Hu S (2003) Chemical cytometry. Curr Opin Chem Biol 7:603–608

    PubMed  CAS  Google Scholar 

  38. Edwards JS, Ibarra RU, Palsson BO (2001) In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data. Nat Biotechnol 19:125–130

    PubMed  CAS  Google Scholar 

  39. Edwards JS, Palsson BO (2000a) The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proc Natl Acad Sci USA 97:5528–5533

    PubMed  CAS  Google Scholar 

  40. Edwards JS, Palsson BO (2000b) Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions. BMC Bioinformatics 1:1

    PubMed  CAS  Google Scholar 

  41. Ellis LB, Hou BK, Kang W, Wackett LP (2003) The University of Minnesota Biocatalysis/Biodegradation Database: post-genomic data mining. Nucleic Acids Res 31:262–265

    PubMed  CAS  Google Scholar 

  42. Ellis LB, Roe D, Wackett LP (2006) The University of Minnesota Biocatalysis/Biodegradation Database: the first decade. Nucleic Acids Res 34:D517–521

    PubMed  CAS  Google Scholar 

  43. Emmerling M, Bailey JE, Sauer U (1999) Glucose catabolism of Escherichia coli strains with increased activity and altered regulation of key glycolytic enzymes. Metab Eng 1:117–127

    PubMed  CAS  Google Scholar 

  44. Fehr M, Ehrhardt DW, Lalonde S, Frommer WB (2004) Minimally invasive dynamic imaging of ions and metabolites in living cells. Curr Opin Plant Biol 7:345–351

    PubMed  CAS  Google Scholar 

  45. Fiehn O (2002) Metabolomics - the link between genotypes and phenotypes. Plant Mol Biol 48:155–171

    PubMed  CAS  Google Scholar 

  46. Fievet JB, Dillmann C, Curien G, de Vienne D (2006) Simplified modelling of metabolic pathways for flux prediction and optimization: lessons from an in vitro reconstruction of the upper part of glycolysis. Biochem J 396:317–326

    PubMed  CAS  Google Scholar 

  47. Fischer E, Sauer U (2003) Metabolic flux profiling of Escherichia coli mutants in central carbon metabolism using GC-MS. Eur J Biochem 270:880–891

    PubMed  CAS  Google Scholar 

  48. Fong SS, Joyce AR, Palsson BO (2005) Parallel adaptive evolution cultures of Escherichia coli lead to convergent growth phenotypes with different gene expression states. Genome Res 15:1365–1372

    PubMed  CAS  Google Scholar 

  49. Fong SS, Marciniak JY, Palsson BO (2003) Description and interpretation of adaptive evolution of Escherichia coli K-12 MG1655 by using a genome-scale in silico metabolic model. J Bacteriol 185:6400–6408

    PubMed  CAS  Google Scholar 

  50. Fong SS, Nanchen A, Palsson BO, Sauer U (2006) Latent pathway activation and increased pathway capacity enable Escherichia coli adaptation to loss of key metabolic enzymes. J Biol Chem 281:8024–8033

    PubMed  CAS  Google Scholar 

  51. Fong SS, Palsson BO (2004) Metabolic gene-deletion strains of Escherichia coli evolve to computationally predicted growth phenotypes. Nat Genet 36:1056–1058

    PubMed  CAS  Google Scholar 

  52. Gerdes S, Edwards R, Kubal M, Fonstein M, Stevens R, Osterman A (2006) Essential genes on metabolic maps. Curr Opin Biotechnol 17:448–456

    PubMed  CAS  Google Scholar 

  53. Giaever G, Chu AM, Ni L, Connelly C, Riles L, Veronneau S, Dow S, Lucau-Danila A, Anderson K, Andre B, Arkin AP, Astromoff A, El-Bakkoury M, Bangham R, Benito R, Brachat S, Campanaro S, Curtiss M, Davis K, Deutschbauer A, Entian KD, Flaherty P, Foury F, Garfinkel DJ, Gerstein M, Gotte D, Guldener U, Hegemann JH, Hempel S, Herman Z, Jaramillo DF, Kelly DE, Kelly SL, Kotter P, LaBonte D, Lamb DC, Lan N, Liang H, Liao H, Liu L, Luo C, Lussier M, Mao R, Menard P, Ooi SL, Revuelta JL, Roberts CJ, Rose M, Ross-Macdonald P, Scherens B, Schimmack G, Shafer B, Shoemaker DD, Sookhai-Mahadeo S, Storms RK, Strathern JN, Valle G, Voet M, Volckaert G, Wang CY, Ward TR, Wilhelmy J, Winzeler EA, Yang Y, Yen G, Youngman E, Yu K, Bussey H, Boeke JD, Snyder M, Philippsen P, Davis RW, Johnston M (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418:387–391

    PubMed  CAS  Google Scholar 

  54. Gibon Y, Usadel B, Blaesing OE, Kamlage B, Hoehne M, Trethewey R, Stitt M (2006) Integration of metabolite with transcript and enzyme activity profiling during diurnal cycles in Arabidopsis rosettes. Genome Biol 7:R76

    PubMed  Google Scholar 

  55. Gill RT (2003) Enabling inverse metabolic engineering through genomics. Curr Opin Biotechnol 14:484–490

    PubMed  CAS  Google Scholar 

  56. Green ML, Karp PD (2004) A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases. BMC Bioinformatics 5:76

    PubMed  Google Scholar 

  57. Harada K, Fukusaki E, Kobayashi A (2006) Pressure-assisted capillary electrophoresis mass spectrometry using combination of polarity reversion and electroosmotic flow for metabolomics anion analysis. J Biosci Bioeng 101:403–409

    PubMed  CAS  Google Scholar 

  58. Hattori M, Okuno Y, Goto S, Kanehisa M (2003) Development of a chemical structure comparison method for integrated analysis of chemical and genomic information in the metabolic pathways. J Am Chem Soc 125:11853–11865

    PubMed  CAS  Google Scholar 

  59. Hirai MY, Yano M, Goodenowe DB, Kanaya S, Kimura T, Awazuhara M, Arita M, Fujiwara T, Saito K (2004) Integration of transcriptomics and metabolomics for understanding of global responses to nutritional stresses in Arabidopsis thaliana. Proc Natl Acad Sci USA 101:10205–10210

    PubMed  CAS  Google Scholar 

  60. Hollywood K, Brison DR, Goodacre R (2006) Metabolomics: Current technologies and future trends. Proteomics 6:4716–4723

    PubMed  CAS  Google Scholar 

  61. Hoque MA, Ushiyama H, Tomita M, Shimizu K (2005) Dynamic responses of the intracellular metabolite concentrations of the wild type and pykA mutant Escherichia coli against pulse addition of glucose or NH3 under those limiting continuous cultures. Biochem Eng J 26:38–49

    CAS  Google Scholar 

  62. Ibarra RU, Edwards JS, Palsson BO (2002) Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth. Nature 420:186–189

    PubMed  CAS  Google Scholar 

  63. Imielinski M, Belta C, Halasz A, Rubin H (2005) Investigating metabolite essentiality through genome-scale analysis of Escherichia coli production capabilities. Bioinformatics 21:2008–2016

    PubMed  CAS  Google Scholar 

  64. Imielinski M, Belta C, Rubin H, Halasz A (2006) Systematic analysis of conservation relations in E. coli genome-scale metabolic network reveals novel growth media. Biophys J 90:2659–2672

    PubMed  CAS  Google Scholar 

  65. Ishii N, Robert M, Nakayama Y, Kanai A, Tomita M (2004) Toward large-scale modeling of the microbial cell for computer simulation. J Biotechnol 113:281–294

    PubMed  CAS  Google Scholar 

  66. Ishii N, Soga T, Nishioka T, Tomita M (2005) Metabolome analysis and metabolic simulation. Metabolomics 1:29–37

    CAS  Google Scholar 

  67. Ito M, Baba T, Mori H (2005) Functional analysis of 1440 Escherichia coli genes using the combination of knock-out library and phenotype microarrays. Metab Eng 7:318–327

    PubMed  CAS  Google Scholar 

  68. Jankowski J, Stephan N, Knobloch M, Fischer S, Schmaltz D, Zidek W, Schluter H (2001) Mass-spectrometry-linked screening of protein fractions for enzymatic activities - a tool for functional genomics. Anal Biochem 290:324–329

    PubMed  CAS  Google Scholar 

  69. Jenkins H, Hardy N, Beckmann M, Draper J, Smith AR, Taylor J, Fiehn O, Goodacre R, Bino RJ, Hall R, Kopka J, Lane GA, Lange BM, Liu JR, Mendes P, Nikolau BJ, Oliver SG, Paton NW, Rhee S, Roessner-Tunali U, Saito K, Smedsgaard J, Sumner LW, Wang T, Walsh S, Wurtele ES, Kell DB (2004) A proposed framework for the description of plant metabolomics experiments and their results. Nat Biotechnol 22:1601–1606

    PubMed  CAS  Google Scholar 

  70. Kaderbhai NN, David I, Broadhurst, Ellis DI, Goodacre R, Kell DB (2003) Functional genomics via metabolic footprinting: monitoring metabolite secretion by Escherichia coli tryptophan metabolism mutants using FT-IR and direct injection electrospray mass spectrometry. Comp Funct Genomics 4:376–391

    PubMed  CAS  Google Scholar 

  71. Kanehisa M, Goto S, Hattori M, Aoki-Kinoshita KF, Itoh M, Kawashima S, Katayama T, Araki M, Hirakawa M (2006) From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res 34:D354–357

    PubMed  CAS  Google Scholar 

  72. Kanehisa M, Goto S, Kawashima S, Nakaya A (2002) The KEGG databases at GenomeNet. Nucleic Acids Res 30:42–46

    PubMed  CAS  Google Scholar 

  73. Kanehisa M, Goto S, Kawashima S, Okuno Y, Hattori M (2004) The KEGG resource for deciphering the genome. Nucleic Acids Res 32:D277–280

    PubMed  CAS  Google Scholar 

  74. Kell DB (2004) Metabolomics and systems biology: making sense of the soup. Curr Opin Microbiol 7:296–307

    PubMed  CAS  Google Scholar 

  75. Kell DB (2006) Theodor Bucher Lecture. Metabolomics, modelling and machine learning in systems biology - towards an understanding of the languages of cells. Delivered on 3 July 2005 at the 30th FEBS Congress and the 9th IUBMB conference in Budapest. FEBS J 273:873–894

    PubMed  CAS  Google Scholar 

  76. Kell DB, Brown M, Davey HM, Dunn WB, Spasic I, Oliver SG (2005) Metabolic footprinting and systems biology: the medium is the message. Nat Rev Microbiol 3:557–565

    PubMed  CAS  Google Scholar 

  77. Keseler IM, Collado-Vides J, Gama-Castro S, Ingraham J, Paley S, Paulsen IT, Peralta-Gil M, Karp PD (2005) EcoCyc: a comprehensive database resource for Escherichia coli. Nucleic Acids Res 33:D334–337

    PubMed  CAS  Google Scholar 

  78. Kharchenko P, Vitkup D, Church GM (2004) Filling gaps in a metabolic network using expression information. Bioinformatics 20(1):I178–I185

    PubMed  CAS  Google Scholar 

  79. Kitagawa M, Ara T, Arifuzzaman M, Ioka-Nakamichi T, Inamoto E, Toyonaga H, Mori H (2005) Complete set of ORF clones of Escherichia coli ASKA library (A Complete Set of E. coli K-12 ORF Archive): Unique Resources for Biological Research. DNA Res 12:291–299

    PubMed  CAS  Google Scholar 

  80. Koek MM, Muilwijk B, van der Werf MJ, Hankemeier T (2006) Microbial metabolomics with gas chromatography/mass spectrometry. Anal Chem 78:1272–1281

    PubMed  CAS  Google Scholar 

  81. Koeniger SL, Merenbloom SI, Valentine SJ, Jarrold MF, Udseth HR, Smith RD, Clemmer DE (2006) An IMS-IMS analogue of MS-MS. Anal Chem 78:4161–4174

    PubMed  CAS  Google Scholar 

  82. Kopka J, Schauer N, Krueger S, Birkemeyer C, Usadel B, Bergmuller E, Dormann P, Weckwerth W, Gibon Y, Stitt M, Willmitzer L, Fernie AR, Steinhauser D (2005) GMD@CSB.DB: the Golm Metabolome Database. Bioinformatics 21:1635–1638

    PubMed  CAS  Google Scholar 

  83. Kramer M, Bongaerts J, Bovenberg R, Kremer S, Muller U, Orf S, Wubbolts M, Raeven L (2003) Metabolic engineering for microbial production of shikimic acid. Metab Eng 5:277–283

    PubMed  CAS  Google Scholar 

  84. Kresnowati MTAP, van Winden WA, Almering MJH, Proell A, Ras C, Knijnenburg TA, Daran-Lapujade PAS, Pronk JT, Heijnen JJ, Daran JM (2006) When transcriptome meets metabolome: fast cellular responses of yeast to sudden relief of glucose limitation. Mol Syst Biol 2:49

    PubMed  CAS  Google Scholar 

  85. Kummel A, Panke S, Heinemann M (2006) Putative regulatory sites unraveled by network-embedded thermodynamic analysis of metabolome data. Mol Syst Biol 2:E1–E10

    Google Scholar 

  86. Kuznetsova E, Proudfoot M, Gonzalez CF, Brown G, Omelchenko MV, Borozan I, Carmel L, Wolf YI, Mori H, Savchenko AV, Arrowsmith CH, Koonin EV, Edwards AM, Yakunin AF (2006) Genome-wide analysis of substrate specificities of the Escherichia coli haloacid dehalogenase-like phosphatase family. J Biol Chem 281:36149–36161

    PubMed  CAS  Google Scholar 

  87. Kuznetsova E, Proudfoot M, Sanders SA, Reinking J, Savchenko A, Arrowsmith CH, Edwards AM, Yakunin AF (2005) Enzyme genomics: Application of general enzymatic screens to discover new enzymes. FEMS Microbiol Rev 29:263–279

    PubMed  CAS  Google Scholar 

  88. Larsson G, Tornkvist M (1996) Rapid sampling, cell inactivation and evaluation of low extracellular glucose concentrations during fed-batch cultivation. J Biotechnol 49:69–82

    PubMed  CAS  Google Scholar 

  89. Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006) A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis. Electrophoresis 27:3306–3321

    PubMed  CAS  Google Scholar 

  90. Lee DY, Yun H, Park S, Lee SY (2003) MetaFluxNet: the management of metabolic reaction information and quantitative metabolic flux analysis. Bioinformatics 19:2144–2146

    PubMed  CAS  Google Scholar 

  91. Lee SY, Lee DY, Kim TY (2005) Systems biotechnology for strain improvement. Trends Biotechnol 23:349–358

    PubMed  CAS  Google Scholar 

  92. Lemke N, Heredia F, Barcellos CK, Dos Reis AN, Mombach JC (2004) Essentiality and damage in metabolic networks. Bioinformatics 20:115–119

    PubMed  CAS  Google Scholar 

  93. Li M, Ho PY, Yao S, Shimizu K (2006) Effect of lpdA gene knockout on the metabolism in Escherichia coli based on enzyme activities, intracellular metabolite concentrations and metabolic flux analysis by (13)C-labeling experiments. J Biotechnol 122:254–266

    PubMed  CAS  Google Scholar 

  94. Liu BF, Xu B, Zhang G, Du W, Luo Q (2006) Micro-separation toward systems biology. J Chromatogr A 1106:19–28

    PubMed  CAS  Google Scholar 

  95. Liu X, Ng C, Ferenci T (2000) Global adaptations resulting from high population densities in Escherichia coli cultures. J Bacteriol 182:4158–4164

    PubMed  CAS  Google Scholar 

  96. Loh KD, Gyaneshwar P, Markenscoff Papadimitriou E, Fong R, Kim KS, Parales R, Zhou Z, Inwood W, Kustu S (2006) A previously undescribed pathway for pyrimidine catabolism. Proc Natl Acad Sci USA 103:5114–5119

    PubMed  CAS  Google Scholar 

  97. Lowry OH, Carter J, Ward JB, Glaser L (1971) The effect of carbon and nitrogen sources on the level of metabolic intermediates in Escherichia coli. J Biol Chem 246:6511–6521

    PubMed  CAS  Google Scholar 

  98. Maharjan RP, Ferenci T (2003) Global metabolite analysis: the influence of extraction methodology on metabolome profiles of Escherichia coli. Anal Biochem 313:145–154

    PubMed  Google Scholar 

  99. Misra RV, Horler RS, Reindl W, Goryanin II, Thomas GH (2005) EchoBASE: an integrated post-genomic database for Escherichia coli. Nucleic Acids Res 33:D329–333

    PubMed  CAS  Google Scholar 

  100. Neidhardt FC, Ingraham JL, Schaechter M (1990) Physiology of the bacterial cell: A molecular approach. Sinauer Associates, Sunderland, MA

    Google Scholar 

  101. Nobeli I, Ponstingl H, Krissinel EB, Thornton JM (2003) A structure-based anatomy of the E. coli metabolome. J Mol Biol 334:697–719

    PubMed  CAS  Google Scholar 

  102. Nobeli I, Thornton JM (2006) A bioinformatician's view of the metabolome. Bioessays 28:534–545

    PubMed  CAS  Google Scholar 

  103. Noteborn HP, Lommen A, van der Jagt RC, Weseman JM (2000) Chemical fingerprinting for the evaluation of unintended secondary metabolic changes in transgenic food crops. J Biotechnol 77:103–114

    PubMed  CAS  Google Scholar 

  104. Ochoa ML, Harrington PB (2005) Chemometric studies for the characterization and differentiation of microorganisms using in situ derivatization and thermal desorption ion mobility spectrometry. Anal Chem 77:854–863

    PubMed  CAS  Google Scholar 

  105. Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, Kanehisa M (1999) KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res 27:29–34

    PubMed  CAS  Google Scholar 

  106. Osterman A (2006) A hidden metabolic pathway exposed. Proc Natl Acad Sci USA 103:5637–5638

    PubMed  CAS  Google Scholar 

  107. Osterman A, Overbeek R (2003) Missing genes in metabolic pathways: a comparative genomics approach. Curr Opin Chem Biol 7:238–251

    PubMed  CAS  Google Scholar 

  108. Paley SM, Karp PD (2006) The pathway tools cellular overview diagram and omics viewer. Nucleic Acids Res 34:3771–3778

    PubMed  CAS  Google Scholar 

  109. Palsson B (2000) The challenges of in silico biology. Nat Biotechnol 18:1147–1150

    PubMed  CAS  Google Scholar 

  110. Pan Z, Raftery D (2007) Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics. Anal Bioanal Chem 387:525–527

    PubMed  CAS  Google Scholar 

  111. Peng L, Arauzo-Bravo MJ, Shimizu K (2004) Metabolic flux analysis for a ppc mutant Escherichia coli based on (13)C-labelling experiments together with enzyme activity assays and intracellular metabolite measurements. FEMS Microbiol Lett 235:17–23

    PubMed  CAS  Google Scholar 

  112. Pharkya P, Nikolaev EV, Maranas CD (2003) Review of the BRENDA Database. Metab Eng 5:71–73

    PubMed  CAS  Google Scholar 

  113. Pohl NL (2005) Functional proteomics for the discovery of carbohydrate-related enzyme activities. Curr Opin Chem Biol 9:76–81

    PubMed  CAS  Google Scholar 

  114. Proudfoot M, Kuznetsova E, Brown G, Rao NN, Kitagawa M, Mori H, Savchenko A, Yakunin AF (2004) General enzymatic screens identify three new nucleotidases in Escherichia coli: Biochemical characterization of SurE, YfbR, and YjjG. J Biol Chem 279:54687–54694

    PubMed  CAS  Google Scholar 

  115. Raamsdonk LM, Teusink B, Broadhurst D, Zhang N, Hayes A, Walsh MC, Berden JA, Brindle KM, Kell DB, Rowland JJ, Westerhoff HV, van Dam K, Oliver SG (2001) A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nat Biotechnol 19:45–50

    PubMed  CAS  Google Scholar 

  116. Rahman M, Hasan MR, Oba T, Shimizu K (2006) Effect of rpoS gene knockout on the metabolism of Escherichia coli during exponential growth phase and early stationary phase based on gene expressions, enzyme activities and intracellular metabolite concentrations. Biotechnol Bioeng 94:585–595

    PubMed  CAS  Google Scholar 

  117. Reed JL, Vo TD, Schilling CH, Palsson BO (2003) An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR). Genome Biol 4:R54

    PubMed  Google Scholar 

  118. Ross-Macdonald P, Coelho PS, Roemer T, Agarwal S, Kumar A, Jansen R, Cheung KH, Sheehan A, Symoniatis D, Umansky L, Heidtman M, Nelson FK, Iwasaki H, Hager K, Gerstein M, Miller P, Roeder GS, Snyder M (1999) Large-scale analysis of the yeast genome by transposon tagging and gene disruption. Nature 402:413–418

    PubMed  CAS  Google Scholar 

  119. Saghatelian A, Cravatt BF (2005) Discovery metabolite profiling - forging functional connections between the proteome and metabolome. Life Sci 77:1759–1766

    PubMed  CAS  Google Scholar 

  120. Saghatelian A, Trauger SA, Want EJ, Hawkins EG, Siuzdak G, Cravatt BF (2004) Assignment of endogenous substrates to enzymes by global metabolite profiling. Biochemistry 43:14332–14339

    PubMed  CAS  Google Scholar 

  121. Saito N, Robert M, Kitamura S, Baran R, Soga T, Mori H, Nishioka T, Tomita M (2006) Metabolomics approach for enzyme discovery. J Proteome Res 5:1979–1987

    PubMed  CAS  Google Scholar 

  122. Salgado H, Gama-Castro S, Peralta-Gil M, Diaz-Peredo E, Sanchez-Solano F, Santos-Zavaleta A, Martinez-Flores I, Jimenez-Jacinto V, Bonavides-Martinez C, Segura-Salazar J, Martinez-Antonio A, Collado-Vides J (2006) RegulonDB (version 5.0): Escherichia coli K-12 transcriptional regulatory network, operon organization, and growth conditions. Nucleic Acids Res 34:D394–397

    PubMed  CAS  Google Scholar 

  123. Sauer U (2004) High-throughput phenomics: experimental methods for mapping fluxomes. Curr Opin Biotechnol 15:58–63

    PubMed  CAS  Google Scholar 

  124. Schaefer U, Boos W, Takors R, Weuster-Botz D (1999) Automated sampling device for monitoring intracellular metabolite dynamics. Anal Biochem 270:88–96

    PubMed  CAS  Google Scholar 

  125. Schaub J, Schiesling C, Reuss M, Dauner M (2006) Integrated sampling procedure for metabolome analysis. Biotechnol Prog 22:1434–1442

    PubMed  CAS  Google Scholar 

  126. Schwab W (2003) Metabolome diversity: too few genes, too many metabolites? Phytochemistry 62:837–849

    PubMed  CAS  Google Scholar 

  127. Serina S, Nozza F, Nicastro G, Faggioni F, Mottl H, Deho G, Polissi A (2004) Scanning the Escherichia coli chromosome by random transposon mutagenesis and multiple phenotypic screening. Res Microbiol 155:692–701

    PubMed  CAS  Google Scholar 

  128. Serres MH, Goswami S, Riley M (2004) GenProtEC: an updated and improved analysis of functions of Escherichia coli K-12 proteins. Nucleic Acids Res 32:D300–302

    PubMed  CAS  Google Scholar 

  129. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504

    PubMed  CAS  Google Scholar 

  130. Shimizu K (2004) Metabolic flux analysis based on 13C-labeling experiments and integration of the information with gene and protein expression patterns. Adv Biochem Eng Biotechnol 91:1–49

    PubMed  CAS  Google Scholar 

  131. Siddiquee KA, Arauzo-Bravo MJ, Shimizu K (2004) Effect of a pyruvate kinase (pykF-gene) knockout mutation on the control of gene expression and metabolic fluxes in Escherichia coli. FEMS Microbiol Lett 235:25–33

    PubMed  CAS  Google Scholar 

  132. Soga T, Baran R, Suematsu M, Ueno Y, Ikeda S, Sakurakawa T, Kakazu Y, Ishikawa T, Robert M, Nishioka T, Tomita M (2006) Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption. J Biol Chem 281:16768–16776

    PubMed  CAS  Google Scholar 

  133. Soga T, Heiger DN (2000) Amino acid analysis by capillary electrophoresis electrospray ionization mass spectrometry. Anal Chem 72:1236–1241

    PubMed  CAS  Google Scholar 

  134. Soga T, Kakazu Y, Robert M, Tomita M, Nishioka T (2004) Qualitative and quantitative analysis of amino acids by capillary electrophoresis-electrospray ionization-tandem mass spectrometry. Electrophoresis 25:1964–1972

    PubMed  CAS  Google Scholar 

  135. Soga T, Ohashi Y, Ueno Y, Naraoka H, Tomita M, Nishioka T (2003) Quantitative metabolome analysis using capillary electrophoresis mass spectrometry. J Proteome Res 2:488–494

    PubMed  CAS  Google Scholar 

  136. Soga T, Ueno Y, Naraoka H, Matsuda K, Tomita M, Nishioka T (2002a) Pressure-assisted capillary electrophoresis electrospray ionization mass spectrometry for analysis of multivalent anions. Anal Chem 74:6224–6229

    PubMed  CAS  Google Scholar 

  137. Soga T, Ueno Y, Naraoka H, Ohashi Y, Tomita M, Nishioka T (2002b) Simultaneous determination of anionic intermediates for Bacillus subtilis metabolic pathways by capillary electrophoresis electrospray ionization mass spectrometry. Anal Chem 74:2233–2239

    PubMed  CAS  Google Scholar 

  138. Spasic I, Dunn WB, Velarde G, Tseng A, Jenkins H, Hardy N, Oliver SG, Kell DB (2006) MeMo: a hybrid SQL/XML approach to metabolomic data management for functional genomics. BMC Bioinformatics 7:281

    PubMed  Google Scholar 

  139. Stephanopoulos G, Alper H, Moxley J (2004) Exploiting biological complexity for strain improvement through systems biology. Nat Biotechnol 22:1261–1267

    PubMed  CAS  Google Scholar 

  140. Strelkov S, von Elstermann M, Schomburg D (2004) Comprehensive analysis of metabolites in Corynebacterium glutamicum by gas chromatography/mass spectrometry. Biol Chem 385:853–861

    PubMed  CAS  Google Scholar 

  141. Sugimoto M, Kikuchi S, Arita M, Soga T, Nishioka T, Tomita M (2005) Large-scale prediction of cationic metabolite identity and migration time in capillary electrophoresis mass spectrometry using artificial neural networks. Anal Chem 77:78–84

    PubMed  CAS  Google Scholar 

  142. Sundararaj S, Guo A, Habibi-Nazhad B, Rouani M, Stothard P, Ellison M, Wishart DS (2004) The CyberCell Database (CCDB): a comprehensive, self-updating, relational database to coordinate and facilitate in silico modeling of Escherichia coli. Nucleic Acids Res 32:D293–295

    PubMed  CAS  Google Scholar 

  143. Szyperski T (1998) 13C-NMR, MS and metabolic flux balancing in biotechnology research. Q Rev Biophys 31:41–106

    PubMed  CAS  Google Scholar 

  144. ter Kuile BH, Westerhoff HV (2001) Transcriptome meets metabolome: hierarchical and metabolic regulation of the glycolytic pathway. FEBS Lett 500:169–171

    PubMed  Google Scholar 

  145. Thimm O, Blasing O, Gibon Y, Nagel A, Meyer S, Kruger P, Selbig J, Muller LA, Rhee SY, Stitt M (2004) MAPMAN: a user-driven tool to display genomics data sets onto diagrams of metabolic pathways and other biological processes. Plant J 37:914–939

    PubMed  CAS  Google Scholar 

  146. Tomita M, Nishioka T (2005) Metabolomics: The frontier of systems biology. Spinger, Tokyo

    Google Scholar 

  147. Tweeddale H, Notley-McRobb L, Ferenci T (1998) Effect of slow growth on metabolism of Escherichia coli, as revealed by global metabolite pool ("metabolome") analysis. J Bacteriol 180:5109–5116

    PubMed  CAS  Google Scholar 

  148. Tweeddale H, Notley-McRobb L, Ferenci T (1999) Assessing the effect of reactive oxygen species on Escherichia coli using a metabolome approach. Redox Rep 4:237–241

    PubMed  CAS  Google Scholar 

  149. Usadel B, Nagel A, Thimm O, Redestig H, Blaesing OE, Palacios-Rojas N, Selbig J, Hannemann J, Piques MC, Steinhauser D, Scheible WR, Gibon Y, Morcuende R, Weicht D, Meyer S, Stitt M (2005) Extension of the visualization tool MapMan to allow statistical analysis of arrays, display of corresponding genes, and comparison with known responses. Plant Physiol 138:1195–1204

    PubMed  CAS  Google Scholar 

  150. Vaidyanathan S (2005) Profiling microbial metabolomes: what do we stand to gain? Metabolomics 1:17–28

    CAS  Google Scholar 

  151. Valet G (2005) Cytomics, the human cytome project and systems biology: top-down resolution of the molecular biocomplexity of organisms by single cell analysis. Cell Prolif 38:171–174

    PubMed  CAS  Google Scholar 

  152. van der Werf MJ, Jellema RH, Hankemeier T (2005) Microbial metabolomics: replacing trial-and-error by the unbiased selection and ranking of targets. J Ind Microbiol Biotechnol 32:234–252

    PubMed  Google Scholar 

  153. Villas-Boas SG, Hojer-Pedersen J, Akesson M, Smedsgaard J, Nielsen J (2005a) Global metabolite analysis of yeast: evaluation of sample preparation methods. Yeast 22:1155–1169

    PubMed  CAS  Google Scholar 

  154. Villas-Boas SG, Mas S, Akesson M, Smedsgaard J, Nielsen J (2005b) Mass spectrometry in metabolome analysis. Mass Spectrom Rev 24:613–646

    PubMed  CAS  Google Scholar 

  155. Wagner C, Sefkow M, Kopka J (2003) Construction and application of a mass spectral and retention time index database generated from plant GC/EI-TOF-MS metabolite profiles. Phytochemistry 62:887–900

    PubMed  CAS  Google Scholar 

  156. Wang QZ, Wu CY, Chen T, Chen X, Zhao XM (2006) Integrating metabolomics into a systems biology framework to exploit metabolic complexity: strategies and applications in microorganisms. Appl Microbiol Biotechnol 70:151–161

    PubMed  CAS  Google Scholar 

  157. Watts KT, Lee PC, Schmidt-Dannert C (2006) Biosynthesis of plant-specific stilbene polyketides in metabolically engineered Escherichia coli. BMC Biotechnol 6:22

    PubMed  Google Scholar 

  158. Wheeler DL, Barrett T, Benson DA, Bryant SH, Canese K, Chetvernin V, Church DM, DiCuccio M, Edgar R, Federhen S, Geer LY, Helmberg W, Kapustin Y, Kenton DL, Khovayko O, Lipman DJ, Madden TL, Maglott DR, Ostell J, Pruitt KD, Schuler GD, Schriml LM, Sequeira E, Sherry ST, Sirotkin K, Souvorov A, Starchenko G, Suzek TO, Tatusov R, Tatusova TA, Wagner L, Yaschenko E (2006) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 34:D173–180

    PubMed  CAS  Google Scholar 

  159. Wiback SJ, Mahadevan R, Palsson BO (2004) Using metabolic flux data to further constrain the metabolic solution space and predict internal flux patterns: the Escherichia coli spectrum. Biotechnol Bioeng 86:317–331

    PubMed  CAS  Google Scholar 

  160. Wittmann C (2002) Metabolic flux analysis using mass spectrometry. Adv Biochem Eng Biotechnol 74:39–64

    PubMed  CAS  Google Scholar 

  161. Wittmann C, Kromer JO, Kiefer P, Binz T, Heinzle E (2004) Impact of the cold shock phenomenon on quantification of intracellular metabolites in bacteria. Anal Biochem 327:135–139

    PubMed  CAS  Google Scholar 

  162. Wu L, Mashego MR, van Dam JC, Proell AM, Vinke JL, Ras C, van Winden WA, van Gulik WM, Heijnen JJ (2005) Quantitative analysis of the microbial metabolome by isotope dilution mass spectrometry using uniformly 13C-labeled cell extracts as internal standards. Anal Biochem 336:164–171

    PubMed  CAS  Google Scholar 

  163. Yu Y, Ko KS, Zea CJ, Pohl NL (2004) Discovery of the chemical function of glycosidases: design, synthesis, and evaluation of mass-differentiated carbohydrate libraries. Org Lett 6:2031–2033

    PubMed  CAS  Google Scholar 

  164. Zamboni N, Sauer U (2004) Model-independent fluxome profiling from 2H and 13C experiments for metabolic variant discrimination. Genome Biol 5:R99

    PubMed  Google Scholar 

  165. Zea CJ, Pohl NL (2004) Kinetic and substrate binding analysis of phosphorylase b via electrospray ionization mass spectrometry: a model for chemical proteomics of sugar phosphorylases. Anal Biochem 327:107–113

    PubMed  CAS  Google Scholar 

  166. Zhou L, Lei XH, Bochner BR, Wanner BL (2003a) Phenotype microarray analysis of Escherichia coli K-12 mutants with deletions of all two-component systems. J Bacteriol 185:4956–4972

    PubMed  CAS  Google Scholar 

  167. Zhou S, Shanmugam KT, Ingram LO (2003b) Functional replacement of the Escherichia coli D-(-)-lactate dehydrogenase gene (ldhA) with the L-(+)-lactate dehydrogenase gene (ldhL) from Pediococcus acidilactici. Appl Environ Microbiol 69:2237–2244

    PubMed  CAS  Google Scholar 

  168. Zhu J, Shimizu K (2004) The effect of pfl gene knockout on the metabolism for optically pure D-lactate production by Escherichia coli. Appl Microbiol Biotechnol 64:367–375

    PubMed  CAS  Google Scholar 

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Robert, M., Soga, T., Tomita, M. (2007). E. coli metabolomics: capturing the complexity of a “simple” model. In: Nielsen, J., Jewett, M.C. (eds) Metabolomics. Topics in Current Genetics, vol 18. Springer, Berlin, Heidelberg. https://doi.org/10.1007/4735_2007_0221

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