A genome-scale metabolic flux model of Escherichia coli K–12 derived from the EcoCyc database

BMC Systems Biology

Peter D Karp²  Ian T Paulsen¹  Amanda Mackie¹  Ingrid M Keseler²  Daniel S Weaver² 

[1] Department of Chemistry and Biomolecular Science, Macquarie University, Balaclava Rd, North Ryde NSW 2109, Australia;Bioinformatics Research Group, SRI International, 333 Ravenswood Ave., 94025 Menlo Park, CA, USA

关键词: Pathway Tools;    EcoCyc;    Systems biology;    Gene essentiality;    Genome-scale model;    Metabolic modeling;    Metabolic network reconstruction;    Constraint-based modeling;    Flux balance analysis;    Escherichia coli;   

Others  :  863163
DOI  :  10.1186/1752-0509-8-79

 received in 2014-03-22, accepted in 2014-06-19,  发布年份 2014

【 摘 要 】

Background

Constraint-based models of Escherichia coli metabolic flux have played a key role in computational studies of cellular metabolism at the genome scale. We sought to develop a next-generation constraint-based E. coli model that achieved improved phenotypic prediction accuracy while being frequently updated and easy to use. We also sought to compare model predictions with experimental data to highlight open questions in E. coli biology.

Results

We present EcoCyc–18.0–GEM, a genome-scale model of the E. coli K–12 MG1655 metabolic network. The model is automatically generated from the current state of EcoCyc using the MetaFlux software, enabling the release of multiple model updates per year. EcoCyc–18.0–GEM encompasses 1445 genes, 2286 unique metabolic reactions, and 1453 unique metabolites. We demonstrate a three-part validation of the model that breaks new ground in breadth and accuracy: (i) Comparison of simulated growth in aerobic and anaerobic glucose culture with experimental results from chemostat culture and simulation results from the E. coli modeling literature. (ii) Essentiality prediction for the 1445 genes represented in the model, in which EcoCyc–18.0–GEM achieves an improved accuracy of 95.2% in predicting the growth phenotype of experimental gene knockouts. (iii) Nutrient utilization predictions under 431 different media conditions, for which the model achieves an overall accuracy of 80.7%. The model’s derivation from EcoCyc enables query and visualization via the EcoCyc website, facilitating model reuse and validation by inspection. We present an extensive investigation of disagreements between EcoCyc–18.0–GEM predictions and experimental data to highlight areas of interest to E. coli modelers and experimentalists, including 70 incorrect predictions of gene essentiality on glucose, 80 incorrect predictions of gene essentiality on glycerol, and 83 incorrect predictions of nutrient utilization.

Conclusion

Significant advantages can be derived from the combination of model organism databases and flux balance modeling represented by MetaFlux. Interpretation of the EcoCyc database as a flux balance model results in a highly accurate metabolic model and provides a rigorous consistency check for information stored in the database.

【 授权许可】

   
2014 Weaver et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 7.

【 参考文献 】

• [1]Orth JD, Thiele I, Palsson BØ: What is flux balance analysis? Nat Biotechnol 2010, 28(3):245-248.
• [2]Thiele I, Palsson BØ: A protocol for generating a high-quality genome-scale metabolic reconstruction. Nat Protoc 2010, 5(1):93-121.
• [3]Edwards J, Palsson BØ: The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proc Natl Acad Sci U S A 2000, 97:5528-5533.
• [4]Reed JL, Vo TD, Schilling CH, Palsson BØ: An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR). Genome Biol 2003, 4(9):54.
• [5]Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BØ: A genome-scale metabolic reconstruction for Escherichia coli K–12 MG1655 that accounts for 1260 ORFs and thermodynamic information. Mol Syst Biol 2007, 3:121.
• [6]Orth JD, Conrad TM, Na J, Lerman JA, Nam H, Feist AM, Palsson BØ: A comprehensive genome-scale reconstruction of Escherichia coli metabolism — 2011. Mol Syst Biol 2011, 7:535.
• [7]Majewski RA, Domach MM: Simple constrained-optimization view of acetate overflow in E. coli. Biotechnol Bioeng 1990, 35(7):732-738.
• [8]Varma A, Boesch BW, Palsson BØ: Biochemical production capabilities ofEscherichia coli. Biotechnol Bioeng 1993, 42(1):59-73.
• [9]Varma A, Palsson BØ: Metabolic capabilities of Escherichia coli: I. synthesis of biosynthetic precursors and cofactors. J Theor Biol 1993, 165(4):477-502.
• [10]Pramanik J, Keasling JD: Stoichiometric model of Escherichia coli metabolism: incorporation of growth-rate dependent biomass composition and mechanistic energy requirements. Biotechnol Bioeng 1997, 56(4):398-421.
• [11]Oberhardt MA, Palsson BØ: Applications of genome-scale metabolic reconstructions. Mol Syst Biol 2009, 5:320.
• [12]Lewis NE, Nagarajan H, Palsson BØ: Constraining the metabolic genotype-phenotype relationship using a phylogeny of in silico methods. Nat Rev Microbiol 2012, 10(4):291-305.
• [13]McCloskey D, Palsson BØ: Basic and applied uses of genome-scale metabolic network reconstructions ofEscherichia coli. Mol Syst Biol 2013, 9:661.
• [14]Keseler IM, Mackie A, Peralta-Gil M, Santos-Zavaleta A, Gama-Castro S, Bonavides-Martinez C, Fulcher C, Huerta AM, Kothari A, Krummenacker M, Latendresse M, Muniz-Rascado L, Ong Q, Paley S, Schroder I, Shearer AG, Subhraveti P, Travers M, Weerasinghe D, Weiss V, Collado-Vides J, Gunsalus RP, Paulsen I, Karp PD: EcoCyc: fusing model organism databases with systems biology. Nucleic Acids Res 2013, 41(Database issue):605-612.
• [15]Latendresse M, Krummenacker M, Trupp M, Karp PD: Construction and completion of flux balance models from pathway databases. Bioinformatics 2012, 28:388-396.
• [16]Karp PD, Paley SM, Krummenacker M, Latendresse M, Dale JM, Lee T, Kaipa P, Gilham F, Spaulding A, Popescu L, Altman T, Paulsen I, Keseler IM, Caspi R: Pathway Tools version 13.0: integrated software for pathway/genome informatics and systems biology. Brief Bioinform 2010, 11:40-79. [doi:10.1093/bib/bbp043]
• [17]O’Brien EJ, Lerman JA, Chang RL, Hyduke DR, Palsson BØ: Genome-scale models of metabolism and gene expression extend and refine growth phenotype prediction. Mol Syst Biol 2013, 9:693.
• [18]Knuth DE: Literate programming. Comput J 1984, 27(2):97-111.
• [19]Mackie A, Keseler IM, Nolan L, Karp PD, Paulsen IT: Dead end metabolites — defining the known unknowns of the E. coli metabolic network. PLoS One 2013, 8(9):75210.
• [20]Schellenberger J, Que R, Fleming RM, Thiele I, Orth JD, Feist AM, Zielinski DC, Bordbar A, Lewis NE, Rahmanian S, Kang J, Hyduke DR, Palsson BØ: Quantitative prediction of cellular metabolism with constraint-based models: the COBRA toolbox v2.0. Nat Protoc 2011, 6:1290-1307.
• [21]Treberg JR, Brand MD: A model of the proton translocation mechanism of complex I. JBC 2011, 286(20):17579-17584.
• [22]Wikstrom M, Hummer G: Stoichiometry of proton translocation by respiratory complex I and its mechanistic implications. PNAS 2012, 109(12):4431-4436.
• [23]Kayser A, Weber J, Hecht V, Rinas U: Metabolic flux analysis of Escherichia coli in glucose-limited continuous culture. i. growth-rate-dependent metabolic efficiency at steady state. Microbiology 2005, 151:693-706.
• [24]Belaich A, Belaich JP: Microcalorimetric study of the anaerobic growth of Escherichia coli: growth thermograms in a synthetic medium. J Bacteriol 1976, 72:497-499.
• [25]Varma A, Boesch BW, Palsson BØ: Stoichiometric interpretation of Escherichia coli glucose catabolism under various oxygenation rates. Appl Environ Microbiol 1993, 59(8):2465-2473.
• [26]Zhuang K, Vemuri GN, Mahadevan R: Economics of membrane occupancy and respiro-fermentation. Mol Syst Biol 2011, 7:500.
• [27]van Hoek MJA, Merks RMH: Redox balance is key to explaining full vs. partial switching to low-yield metabolism. BMC Syst Biol 2012, 6:22.
• [28]Ibarra RU, Edwards JS, Palsson BØ: Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth. Nature 2002, 420:186-189.
• [29]Milne CB, Kim PJ, Eddy JA, Price ND: Accomplishments in genome-scale in silico modeling for industrial and medical biotechnology. Biotechnol J 2009, 4(12):1653-16570.
• [30]Gianchandani EP, Chavali AK, Papin JA: The application of flux balance analysis in systems biology. WIREs Syst Biol Med 2010, 2(3):372-382.
• [31]Lee JW, Na D, Park JM, Lee J, Choi S, Lee SY: Systems metabolic engineering of microorganisms for natural and non-natural chemicals. Nat Chem Biol 2012, 8:536-546.
• [32]Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL: Construction of Escherichia coli K–12 in-frame, single-gene knockout mutants: The Keio collection. Mol Syst Biol 2006, 2(2006):0008.
• [33]Yamamoto N, Nakahigashi K, Nakamichi T, Yoshino M, Takai Y, Touda Y, Furubayashi A, Kinjyo S, Dose H, Hasegawa M, Datsenko KA, Nakayashiki T, Tomita M, Wanner BL, Mori H: Update on the collection of Escherichia coli single-gene deletion mutants. Mol Syst Biol 2009, 5:335.
• [34]Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BØ: Experimental and computational assessment of conditionally essential genes in Escherichia coli. J Bacteriol 2006, 188(23):8259-8271.
• [35]Cox RJ, Wang PSH: Is N-acetylornithine aminotransferase the real N-succinyl-LL-diaminopimelate aminotransferase in Escherichia coli andMycobacterium smegmatis? J Chem Soc, Perkin Trans 2001, 1:2006-2008.
• [36]Kim J, Copley S: Why metabolic enzymes are essential or nonessential for growth of Escherichia coli K–12 on glucose. Biochemistry 2007, 46(44):12501-12511.
• [37]van der Ploeg JR, Eichhorn E, Leisinger T: Sulfonate-sulfur metabolism and its regulation in Escherichia coli. Arch Microbiol 2001, 176:1-8.
• [38]Bykowski T, van der Ploeg JR, Iwanicka-Nowicka R, Hryniewicz MM: The switch from inorganic to organic sulphur assimilation in Escherichia coli: adenosine 5’-phosphosulphate (APS) as a signalling molecule for sulphate excess. Mol Microbiol 2002, 43(5):1347-1358.
• [39]Richaud C, Higgins W, Mengin-Lecruelx D, Stragier P: Molecular cloning, characterization, and chromosomal localization of dapF, the Escherichia coli gene for diaminopimelate epimerase. J Bacteriol 1987, 169(4):1454-1459.
• [40]Mengin-Lecruelx D, Michaud C, Richaud C, Blanot D, van Heijenoort J: Incorporation of LL-diaminopimelic acid into peptidoglycan of Escherichia coli mutants lacking diaminopimelate epimerase encoded by dapF. J Bacteriol 1988, 170(5):2031-2039.
• [41]el-Hajj HH, Zhang H, Weiss B: Lethality of a dut (deoxyuridine triphosphatase) mutation in Escherichia coli. J Bacteriol 1988, 170(3):1069-1075.
• [42]Gross M, Marianovsky I, Glaser G: MazG - a regulator of programmed cell death in Escherichia coli. Mol Microbiol 2006, 59(2):590-601.
• [43]Haussmann C, Rohdich F, Schmidt E, Bacher A, Richter G: Biosynthesis of pteridines in Escherichia coli. Structural and mechanistic similarity of dihydroneopterin-triphosphate epimerase and dihydroneopterin aldolase. J Biol Chem 1998, 273(28):17418-17424.
• [44]Kato J, Hashimoto M: Construction of consecutive deletions of the Escherichia coli chromosome. Mol Syst Biol 2007, 3:132.
• [45]Fermer C, Swedberg G: Adaptation to sulfonamide resistance in Neisseria meningitidis may have required compensatory changes to retain enzyme function: kinetic analysis of dihydropteroate synthases from N. meningitidis expressed in a knockout mutant of Escherichia coli. J Bacteriol 1997, 179(3):831-837.
• [46]Inoue A, Murata Y, Takahashi H, Tsuji N, Fujisaki S, Kato J: Involvement of an essential gene,mviN, in murein synthesis inEscherichia coli. J Bacteriol 2008, 190(21):7298-7301.
• [47]Ruiz N: Bioinformatics identification of MurJ (MviN) as the peptidoglycan lipid II flippase in Escherichia coli. PNAS 2008, 105(21):15553-15557.
• [48]Mohammadi T, van Dam V, Sijbrandi R, Vernet T, Zapun A, Bouhss A, MD-d Bruin, Nguyen-Disteche M, de Kruijff B: Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane. EMBO J 2011, 30(8):1425-1432.
• [49]Jermy A: Bacterial physiology: flipping lipids. Nat Rev Microbiol 2011, 9(5):314.
• [50]Butler EK, Davis RM, Bari V, Nicholson PA, Ruiz N: Structure-function analysis of MurJ reveals a solvent-exposed cavity containing residues essential for peptidoglycan biogenesis inEscherichia coli. J Bacteriol 2013, 195(20):4639-4649.
• [51]Sperandeo P, Pozzi C, Deho G, Polissi A: Non-essential kdo biosynthesis and new essential cell envelope biogenesis genes in the Escherichia coli yrbG-yhbG locus. Res Microbiol 2006, 157(6):547-558.
• [52]Mamat U, Meredith TC, Aggarwal P, Kuhl A, Kirchoff P, Lindner B, Hanuszkiewicz A, Sun J, Holst O, Woodard RW: Single amino acid substitutions in either YhjD or MsbA confer viability to 3-deoxy-d-manno-oct-2-ulosonic acid-depleted Escherichia coli. Mol Microbiol 2008, 67(3):633-648.
• [53]Klein G, Lindner B, Brabetz W, Brade H, Raina S: Escherichia coli, K–12 suppressor-free mutants lacking early glycosyltransferases and late acyltransferases: minimal lipopolysaccharide structure and induction of envelope stress response. J Biol Chem 2008, 284(23):15369-151389.
• [54]Green JM, Merkel WK, Nichols BP: Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. J Bacteriol 1992, 174(16):5317-5323.
• [55]Langley D, Guest JR: Biochemical genetics of the α-keto acid dehydrogenase complexes of Escherichia coli K–12: Isolation and biochemical properties of deletion mutants. J Gen Microbiol 1977, 99:263-276.
• [56]Chang YY, Cronan JE: Mapping nonselectable genes of Escherichia coli by using transposon Tn10: location of a gene affecting pyruvate oxidase. J Bacteriol 1982, 151(3):1279-1289.
• [57]Abdel-Hamid AM, Attwood MM, Guest JR: Pyruvate oxidase contributes to the aerobic growth efficiency of Escherichia coli. Microbiology 2001, 147:1483-1498.
• [58]Hillman JD, Fraenkel DG: Glyceraldehyde 3-phosphate dehydrogenase mutants of Escherichia coli. J Bacteriol 1975, 122(3):1175-1179.
• [59]Irani M, Maitra PK: Properties of Escherichia coli mutants deficient in enzymes of glycolysis. J Bacteriol 1977, 132(2):398-410.
• [60]Reeves HC, Ajl SJ: Alpha-hydroxyglutaric acid synthetase. J Bacteriol 1962, 84:186-187.
• [61]Wegener WS, Reeves HC, Ajl SJ: Heterogeneity of the glyoxylate-condensing enzymes. J Bacteriol 1965, 90(3):594-598.
• [62]Helling RB, Kukora JS: Nalidixic acd-resistant mutants of Escherichia coli deficient in isocitrate dehydrogenase. J Bacteriol 1971, 105(3):1224-1226.
• [63]Lakshmi TM, Helling RB: Selection for citrate synthase deficiency in icd mutants of Escherichia coli. J Bacteriol 1976, 127(1):76-83.
• [64]Kabir MM, Shimizu K: Metabolic regulation analysis of icd-gene knockout Escherichia coli based on 2d electrophoresis with maldi-tof mass spectrometry and enzyme activity measurements. Appl Microbiol Biotechnol 2004, 65(1):84-96.
• [65]Lin H, Bennett GN, San KY: Genetic reconstruction of the aerobic central metabolism in Escherichia coli for the absolute aerobic production of succinate. Biotechnol Bioeng 2005, 89(2):148-156.
• [66]Kalliri E, Mulrooney SB, Hausinger RP: Identification of Escherichia coli ygaF as an L-2-hydroxyglutarate oxidase. J Bacteriol 2008, 190(11):3793-3798.
• [67]Reinoso CA, Appanna VD, Vasquez CC: α-ketoglutarate accumulation is not dependent on isocitrate dehydrogenase activity during tellurite detoxification in Escherichia coli. Biomed Res Int 2013, 2013:784190.
• [68]Stribling D, Perham RN: Purification and characterization of two fructose diphosphate aldolases from Escherichia coli (Crookes’ strain). Biochem J 1973, 131(4):833-841.
• [69]Scamuffa MD, Caprioli RM: Comparison of the mechanisms of two distinct aldolases from Escherichia coli grown on gluconeogenic substrates. Biochim Biophys Acta 1980, 614(2):583-590.
• [70]Schurmann M, Sprenger GA: Fructose-6-phosphate aldolase is a novel class I aldolase from Escherichia coli and is related to a novel group of bacterial transaldolases. JBC 2001, 276:11055-11061.
• [71]Baechler C, Schneider P, Baehler P, Lustig A, Erni B: Escherichia coli dihydroxyacetone kinase controls gene expression by binding to transcription factor dhaR. EMBO J 2005, 24(2):283-293.
• [72]Gerike U, Hough DW, Russell NJ, Dyall-Smith ML, Danson MJ: Citrate synthase and 2-methylcitrate synthase: structural, functional and evolutionary relationships. Microbiology 1998, 144(4):929-935.
• [73]Orth JD, Palsson B: Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions. BMC Syst Biol 2012, 6:30.
• [74]Kotlarz D, Garreau H, Buc H: Regulation of the amount and of the activity of phosphofructokinases and pyruvate kinases in Escherichia coli. Biochim Biophys Acta 1975, 381(2):257-268.
• [75]Lovingshimer MR, Siegele D, Reinhart GD: Construction of an inducible, pfkA and pfkB deficient strain of Escherichia coli for the expression and purification of phosphofructokinase from bacterial sources. Protein Expr Purif 2006, 46:475-482.
• [76]Peng L, Arauzo-Bravo MJ, Shimizu K: Metabolic flux analysis for a ppc mutant Escherichia coli based on 13C-labelling experiments together with enzyme activity assays and intracellular metabolite measurements. FEMS Microbiol Lett 2004, 235(1):17-23.
• [77]Patrick WM, Quandt EM, Swartzlander DB, Matsumura I: Multicopy suppression underpins metabolic evolvability. Mol Biol Evol 2007, 24(12):2716-2722.
• [78]Ferguson GP, Totemeyer S, MacLean MJ, Booth IR: Methylglyoxal production in bacteria: suicide or survival? Arch Microbiol 1998, 170(4):209-219.
• [79]Fong SS, Nanchen A, Palsson BØ: Latent pathway activation and increased pathway capacity enable Escherichia coli adaptation to loss of key metabolic enzymes. J Biol Chem 2006, 281(12):8024-8033.
• [80]Michel G, Roszak AW, Sauve V, Maclean J, Matte A, Coggins JR, Cygler M, Lapthorn AJ: Structures of shikimate dehydrogenase AroE and its paralog YdiB. a common structural framework for different activities. J Biol Chem 2003, 278(21):19463-19472.
• [81]Johansson L, Liden G: Transcriptome analysis of a shikimic acid producing strain of Escherichia coli W3110 grown under carbon- and phosphate-limited conditions. J Biotechnol 2006, 126(4):528-545.
• [82]Guilloton MB, Lamblin AF, Kozliak EI, Gerami-Nejad M, Tu C, Silverman D, Anderson PM, Fuchs JA: A physiological role for cyanate-induced carbonic anhydrase in Escherichia coli. J Bacteriol 1993, 175(5):1443-1451.
• [83]Howell EE, Foster PG, Foster LM: Construction of a dihydrofolate reductase-deficient mutant of Escherichia coli by gene replacement. J Bacteriol 1988, 170(7):3040-3045.
• [84]Pribat A, Blaby IK, Lara-Núñez A, Gregory JF3rd, de Crécy-Lagard V: FolX and FolM are essential for tetrahydromonapterin synthesis in Escherichia coli and Pseudomonas aeruginosa. J Bacteriol 2010, 192(2):475-482.
• [85]Shim JH, Benkovic SJ: Evaluation of the kinetic mechanism of Escherichia coli glycinamide ribonucleotide transformylase. Biochemistry 1998, 37(24):8776-8782.
• [86]Newman EB, Kapoor V, Potter R: Role of L-threonine dehydrogenase in the catabolism of threonine and synthesis of glycine by Escherichia coli. J Bacteriol 1976, 126(3):1245-1249.
• [87]Liu JQ, Dairi T, Itoh N, Kataoka M, Shimizu S, Yamada H: Gene cloning, biochemical characterization and physiological role of a thermostable low-specificity L-threonine aldolase from Escherichia coli. Eur J Biochem 1998, 255(1):220-226.
• [88]Vales LD, Chase JW, Murphy JB: Orientation of the guanine operon of Escherichia coli K–12 by utilizing strains containing guaB-xse and guaB-upp deletions. J Bacteriol 1979, 139(1):320-322.
• [89]Umbarger HE, Brown B: Threonine deamination in Escherichia coli. II. Evidence for two L-threonine deaminases. J Bacteriol 1957, 73(1):105-112.
• [90]Zhao X, Miller JR, Jiang Y, Marletta MA, Cronan JE: Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem Biol 2003, 10(12):1293-1302.
• [91]Reidl J, Boos W: The malX malY operon of Escherichia coli encodes a novel enzyme II of the phosphotransferase system recognizing glucose and maltose and an enzyme abolishing the endogenous induction of the maltose system. J Bacteriol 1991, 173(15):4862-4876.
• [92]Zdych E, Peist R, Reidl J, Boos W: MalY of Escherichia coli is an enzyme with the activity of a beta C-S lyase (cystathionase). J Bacteriol 1995, 177(17):5035-5039.
• [93]Boos W, Shuman H: Maltose/maltodextrin system of Escherichia coli: transport, metabolism, and regulation. Microbiol Mol Biol Rev 1998, 62(1):204-229.
• [94]Cohen GN, Stanier RY, Bras GL: Regulation of the biosynthesis of amino acids of the aspartate family in coliform bacteria and pseudomonads. J Bacteriol 1969, 99(3):791-801.
• [95]Garriga X, Eliasson R, Torrents E, Jordan A, Barbe J, Gibert I, Reichard P: nrdD and nrdG genes are essential for strict anaerobic growth of Escherichia coli. Biochem Biophys Res Commun 1996, 229(1):189-192.
• [96]Lam HM, Winkler ME: Metabolic relationships between pyridoxine (vitamin B6) and serine biosynthesis in Escherichia coli K–12. J Bacteriol 1990, 172(11):6518-6528.
• [97]Kim J, Kershner JP, Novikov Y, Shoemaker RK, Copley SD: Three serendipitous pathways in E. coli can bypass a block in pyridoxal-5’-phosphate synthesis. Mol Syst Biol 2010, 6:436.
• [98]Hove-Jensen B, Rosenkrantz TJ, Zechel DL, Willemoes M: Accumulation of intermediates of the carbon-phosphorus lyase pathway for phosphonate degradation in phn mutants of Escherichia coli. J Bacteriol 2010, 192(1):370-374.
• [99]Zhang Q, van der Donk WA: Answers to the carbon-phosphorus lyase conundrum. Chembiochem 2012, 13(5):627-629.
• [100]Wanner BL: Gene regulation by phosphate in enteric bacteria. J Cell Biochem 1993, 51(1):47-54.
• [101]Wanner BL, Boline JA: Mapping and molecular cloning of the phn (psiD) locus for phosphonate utilization in Escherichia coli. J Bacteriol 1990, 172(3):1186-1196.
• [102]Ravnikar PD, Somerville RL: Genetic characterization of a highly efficient alternate pathway of serine biosynthesis in Escherichia coli. J Bacteriol 1987, 169(6):2611-2617.
• [103]Kim C, Song S, Park C: The D-allose operon of Escherichia coli K–12. J Bacteriol 1997, 179(24):7631-7637.
• [104]Poulsen TS, Chang YY, Hove-Jensen B: D-allose catabolism of Escherichia coli : involvement of alsI and regulation of als regulon expression by allose and ribose. J Bacteriol 1999, 181(22):7126-7130.
• [105]Pittard J, Wallace BJ: Distribution and function of genes concerned with aromatic biosynthesis inEscherichia coli. J Bacteriol 1966, 91(4):1494-1508.
• [106]Bottomley JR, Clayton CL, Chalk PA, Kleanthous C: Cloning, sequencing, expression, purification, and preliminary characterization of a type II dehydroquinase from Helicobacter pylori. Biochem J 1996, 319(2):559-565.
• [107]von Meyenburg K, Jorgensen BB, Nielsen J, Hansen FG: Promoters of the atp operon coding for the membrane-bound ATP synthase of Escherichia coli mapped by Tn10 insertion mutations. Mol Gen Genet 1982, 188(2):240-248.
• [108]Jensen PR, Michelsen O: Carbon and energy metabolism of atp mutants of Escherichia coli. J Bacteriol 1992, 174(23):7635-7641.
• [109]Green GN, Gennis RB: Isolation and characterization of an Escherichia coli mutant lacking cytochrome d terminal oxidase. J Bacteriol 1983, 154(3):1269-1275.
• [110]Georgiou CD, Fang H, Gennis RB: Identification of the cydC locus required for expression of the functional form of the cytochrome d terminal oxidase complex in Escherichia coli. J Bacteriol 1987, 169(5):2107-2112.
• [111]Puustinen A, Finel M, Haltia T, Gennis RB, Wikstrom M: Properties of the two terminal oxidases of Escherichia coli. Biochemistry 1991, 30(16):3936-3942.
• [112]Pittman MS, Robinson HC, Poole RK: A bacterial glutathione transporter (Escherichia coli CydDC) exports reductant to the periplasm. J Biol Chem 2005, 280(37):32254-32261.
• [113]Portnoy VA, Herrgard MJ, Palsson BØ: Aerobic fermentation of d-glucose by an evolved cytochrome oxidase-deficient Escherichia coli strain. Appl Environ Microbiol 2008, 74(24):7561-7569.
• [114]Borisov VB, Gennis RB, Hemp J, Verkhovsky MI: The cytochrome bd respiratory oxygen reductases. Biochim Biophys Acta 2011, 1807(11):1398-1413.
• [115]Chou CH, Bennett GN, San KY: Effect of modified glucose uptake using genetic engineering techniques on high-level recombinant protein production in Escherichia coli dense cultures. Biotechnol Bioeng 1994, 44(8):952-960.
• [116]Flores N, Xiao J, Berry A, Bolivar F, Valle F: Pathway engineering for the production of aromatic compounds in Escherichia coli. Nat Biotechnol 1996, 14(5):620-623.
• [117]Chen R, Yap WM, Postma PW, Bailey JE: Comparative studies of Escherichia coli strains using different glucose uptake systems: metabolism and energetics. Biotechnol Bioeng 1997, 56(5):583-590.
• [118]Zeppenfeld T, Larisch C, Lengeler JW, Jahreis K: Glucose transporter mutants of Escherichia coli K-12 with changes in substrate recognition of IICB(Glc) and induction behavior of the ptsG gene. J Bacteriol 2000, 182(16):4443-4452.
• [119]Flores N, Flores S, Escalante A, de Anda R: Adaptation for fast growth on glucose by differential expression of central carbon metabolism and gal regulon genes in an Escherichia coli strain lacking the phosphoenolpyruvate:carbohydrate phosphotransferase system. Metab Eng 2005, 7(2):70-87.
• [120]Steinsiek S, Bettenbrock K: Glucose transport in Escherichia coli mutant strains with defects in sugar transport systems. J Bacteriol 2012, 194(21):5897-5908.
• [121]Escalante A, Cervantes AS, Gosset G, Bolivar F: Current knowledge of theEscherichia coli phosphoenolpyruvate-carbohydrate phosphotransferase system: peculiarities of regulation and impact on growth and product formation. Appl Microbiol Biotechnol 2012, 94(6):1483-1494.
• [122]Sarubbi E, Rudd KE, Cashel M: Basal ppgpp level adjustment shown by new spoT mutants affect steady state growth rates and rrnA ribosomal promoter regulation in Escherichia coli. Mol Gen Genet 1988, 213(2–3):214-222.
• [123]Sarubbi E, Rudd KE, Xiao H, Ikehara K, Kalman M, Cashel M: Characterization of the spoT gene of Escherichia coli. J Biol Chem 1989, 264(25):15074-15082.
• [124]Xiao H, Kalman M, Ikehara K, Zemel S, Glaser G, Cashel M: Residual guanosine 3’,5’-bispyrophosphate synthetic activity of relA null mutants can be eliminated by spoT null mutations. J Biol Chem 1991, 266(9):5980-5990.
• [125]Gentry DR, Cashel M: Mutational analysis of the Escherichia coli spoT gene identifies distinct but overlapping regions involved in ppgpp synthesis and degradation. Mol Microbiol 1996, 19(6):1373-1384.
• [126]Jin DJ, Cagliero C, Zhou YN: Growth rate regulation in Escherichia coli. FEMS Microbiol Rev 2012, 36(2):269-287.
• [127]Cox GB, Gibson F, Pittard J: Mutant strains of Escherichia coli K–12 unable to form ubiquinone. J Bacteriol 1968, 95(5):1591-1598.
• [128]Wu G, Williams HD, Gibson F, Poole RK: Mutants of Escherichia coli affected in respiration: the cloning and nucleotide sequence of ubiA, encoding the membrane-bound p-hydroxybenzoate:octaprenyltransferase. J Gen Microbiol 1993, 139(8):1795-1805.
• [129]Klena JD, Ashford RS, Schnaitman CA: Role of Escherichia coli K-12 rfa genes and the rfp gene of Shigella dysenteriae 1 in generation of lipopolysaccharide core heterogeneity and attachment of o antigen. J Bacteriol 1992, 174(22):7297-7307.
• [130]Roncero C, Casadaban MJ: Genetic analysis of the genes involved in synthesis of the lipopolysaccharide core in Escherichia coli K–12: three operons in the rfa locus. J Bacteriol 1992, 174(10):3250-3260.
• [131]Hwang J, Inouye M: The tandem GTPase, der, is essential for the biogenesis of 50S ribosomal subunits in Escherichia coli. Mol Microbiol 2006, 61(6):1660-1672.
• [132]Bharat A, Jiang M, Sullivan SM, Maddock JR, Brown ED: Cooperative and critical roles for both G domains in the GTPase activity and cellular function of ribosome-associated Escherichia coli EngA. J Bacteriol 2006, 188(22):7992-7996.
• [133]Tomar SK, Dhimole N, Chatterjee M, Prakash B: Distinct GDP/GTP bound states of the tandem G-domains of EngA regulate ribosome binding. Nucleic Acids Res 2009, 37(7):2359-2370.
• [134]Spratt BG: Distinct penicillin binding proteins involved in the division, elongation, and shape of Escherichia coli K–12. PNAS 2009, 72(8):2999-3003.
• [135]Ogura T, Bouloc P, Niki H, D’Ari R, Hiraga S, Jaffe A: Penicillin-binding protein 2 is essential in wild-type Escherichia coli but not in lov or cya mutants. J Bacteriol 1989, 171(6):3025-3030.
• [136]Wang Y, Stieglitz KA, Bubunenko M, Court DL, Stec B, Roberts MF: The structure of the R184A mutant of the inositol monophosphatase encoded by suhB and implications for its functional interactions in Escherichia coli. J Biol Chem 2007, 282(37):26989-26996.
• [137]Puan KJ, Wang H, Dairi T, Kuzuyama T, Morita CT: fldA is an essential gene required in the 2-C-methyl-D-erythritol 4-phosphate pathway for isoprenoid biosynthesis. FEBS Lett 2005, 579(17):3802-3806.
• [138]Lu Q, Inouye M: Adenylate kinase complements nucleoside diphosphate kinase deficiency in nucleotide metabolism. PNAS 1996, 93(12):5720-5725.
• [139]Gerhart JC, Schachman HK: Distinct subunits for the regulation and catalytic activity of aspartate transcarbamylase. Biochemistry 1965, 4(6):1054-1062.
• [140]Reed JL, Patel TR, Chen KH, Joyce AR, Applebee MK, Herring CD, Bui OT, Knight EM, Fong SS, Palsson BØ: Systems approach to refining genome annotation. Proc Natl Acad Sci U S A 2006, 103(46):17480-17484.
• [141]Kumar VS, Dasika MS, Maranas CD: Optimization based automated curation of metabolic reconstructions. BMC Bioinformatics 2007, 8:212.
• [142]Kumar VS, Maranas CD: GrowMatch: An automated method for reconciling in silico/in vivo growth predictions. PLoS Comput Biol 2009, 5(3):1000308.
• [143]Barua D, Kim J, Reed JL: An automated phenotype-driven approach (geneforce) for refining metabolic and regulatory models. PLoS Comput Biol 2010, 6(10):1000970.
• [144]Orth JD, Palsson BØ: Systematizing the generation of missing metabolic knowledge. Biotechnol Bioeng 2010, 107(3):403-412.
• [145]Tervo CJ, Reed JL: BioMog: a computational framework for the de novo generation or modification of essential biomass components. PLoS One 2013, 8(12):81322.
• [146]Monod J: The growth of bacterial cultures. Annu Rev Microbiol 1949, 3:371-394.
• [147]Bochner BR, Gadzinski P, Panomitros E: Phenotype microarrays for high-throughput phenotypic testing and assay of gene function. Genome Res 2001, 11(7):1246-1255.
• [148]Shea A, Wolcott M, Daefler S, Rozak DA: Biolog phenotype microarrays. In Microbial Systems Biology: Methods and Protocols. New York: Humana Press; 2012:331-73. Chap. 12
• [149]Mackie AM, Hassan KA, Paulsen IT, Tetu SG: Biolog phenotype microarrays for phenotypic characterization of microbial cells. Methods Mol Biol 1096, 2014:123-301.
• [150]Oun MA, Suthers PF, Jones GI, Carter BR, Saunders MP, Maranas CD, Woodward MJ, Anjum MF: Genome scale reconstruction of a salmonella metabolic model: comparison of similarity and differences with a commensal Escherichia coli strain. J Biol Chem 2009, 284(43):29480-29488.
• [151]Yoon SH, Han MJ, Jeong H, Lee CH, Xia XX, Lee DH, Shim JH, Lee SY, Oh TK, Kim JF: Comparative multi-omics systems analysis of Escherichia coli strains B and K–12. Genome Biol 2012, 13(5):37.
• [152]Mackie A, Paley S, Keseler IM, Shearer A, Paulsen IT, Karp PD: Addition of Escherichia coli K–12 growth-observation and gene essentiality data to the EcoCyc database. J Bacteriol 2014, 196(5):982-988.
• [153]Wilson DM, Wilson TH: Cation specificity for sugar substrates of the melibiose carrier in Escherichia coli. Biochim Biophys Acta 1987, 904(2):191-200.
• [154]Sandermann H Jr: β-D-galactoside transport in Escherichia coli: substrate recognition. Eur J Biochem 1977, 80(2):507-515.
• [155]Sahota SS, Bramley PM, Menzies IS: The fermentation of lactulose by colonic bacteria. Microbiology 1981, 128(2):319-325.
• [156]Wallenfels K, Weil R: β-galactosidase. In The Enzymes, 3rd Ed. New York: Academic Press; 1972:617-663.
• [157]Roderick SL: The lac operon galactoside acetyltransferase. CR Biologies 2005, 328:568-575.
• [158]Lang VJ, Leystra-Lantz C, Cook RA: Characterization of the specific pyruvate transport system in Escherichia coli K–12. J Bacteriol 1987, 169(1):380-385.
• [159]Kim OB, Reimann J, Lukas H, Schumacher U, Grimpo J, Dunnwald P, Unden G: Regulation of tartrate metabolism by TtdR and relation to the DcuS/DcuR-regulated C4-dicarboxylate metabolism of Escherichia coli. Microbiol 2009, 155(11):3632-3640.
• [160]Lukas H, Reimann J, Kim OB, Grimpo J, Unden G: Regulation of aerobic and anaerobic d-malate metabolism of Escherichia coli by the LysR-type regulator DmlR (YeaT). J Bacteriol 2010, 192(10):2503-2511.
• [161]Lauritzen AM, Lipscomb WN: Modification of three active site lysine residues in the catalytic subunit of aspartate transcarbamylase by D- and L-bromosuccinate. J Biol Chem 1982, 257:1312-1319.
• [162]Hall BG: Chromosomal mutation for citrate utilization by Escherichia coli K–12. J Bacteriol 1982, 151(1):269-273.
• [163]Lutgens M, Gottschalk G: Why a co-substrate is required for anaerobic growth of Escherichia coli on citrate. J Gen Microbiol 1980, 119(1):63-70.
• [164]Schneider BL, Ruback S, Kiupakis AK, Kasbarian H, Pybus C, Reitzer L: The Escherichia coli gabDTPC operon: specific gamma-aminobutyrate catabolism and nonspecific induction. J Bacteriol 2002, 184(24):6976-6986.
• [165]Cunin R, Glansdorff N, Pierard A, Stalon V: Biosynthesis and metabolism of arginine in bacteria. Microbiol Rev 1986, 50(3):314-352.
• [166]Schneider BL, Kiupakis AK, Reitzer LJ: Arginine catabolism and the arginine succinyltransferase pathway in Escherichia coli. J Bacteriol 1998, 180(16):4278-4286.
• [167]Plumbridge J, Pellegrini O: Expression of the chitobiose operon of Escherichia coli is regulated by three transcription factors: NagC, ChbR and CAP. Mol Microbiol 2004, 52(2):437-449.
• [168]Kachroo AH, Kancherla AK, Singh NS, Varshney U, Mahadevan S: Mutations that alter the regulation of the chb operon of Escherichia coli allow utilization of cellobiose. Mol Microbiol 2007, 66(2):1382-1395.
• [169]Chang GW, Chang JT: Evidence for the B12-dependent enzyme ethanolamine deaminase inSalmonella. Nature 1975, 254(5496):150-151.
• [170]Jones PW, Turner JM: Interrelationships between the enzymes of ethanolamine metabolism in Escherichia coli. J Gen Microbiol 1984, 130(2):299-308.
• [171]Blackwell CM, Turner JM: Microbial metabolism of amino alcohols. formation of coenzyme B12-dependent ethanolamine ammonia-lyase and its concerted induction in Escherichia coli. Biochem J 1978, 176(3):751-757.
• [172]Akita K, Hieda N, Baba N, Kawaguchi S, Sakamoto H, Nakanishi Y, Yamanishi M, Mori K, Toraya T: Purification and some properties of wild-type and N-terminal-truncated ethanolamine ammonia-lyase of Escherichia coli. J Biochem 2010, 147(1):83-93.
• [173]Xi H, Schneider BL, Reitzer L: Purine catabolism in Escherichia coli and function of xanthine dehydrogenase in purine salvage. J Bacteriol 2000, 182(19):5332-5341.
• [174]Reitzer L: Nitrogen assimilation and global regulation in Escherichia coli. Annu Rev Microbiol 2003, 57:155-176.
• [175]Cusa E, Obradors N, Baldoma L, Badia J, Aguilar J: Genetic analysis of a chromosomal region containing genes required for assimilation of allantoin nitrogen and linked glyoxylate metabolism in Escherichia coli. J Bacteriol 1999, 181(24):7479-7484.
• [176]Harborne NR, Griffiths L, Busby SJ, Cole JA: Transcriptional control, translation and function of the products of the five open reading frames of the Escherichia coli nir operon. Mol Microbiol 1992, 6(19):2805-2813.
• [177]Wang H, Tseng CP, Gunsalus RP: The napF and narG nitrate reductase operons in Escherichia coli are differentially expressed in response to submicromolar concentrations of nitrate but not nitrite. J Bacteriol 1999, 181(17):5303-5308.
• [178]Bertero MG, Rothery RA, Palak M, Hou C, Lim D, Blasco F, Weiner JH, Strynadka NC: Insights into the respiratory electron transfer pathway from the structure of nitrate reductase A. Nat Struct Biol 2003, 10(9):681-687.
• [179]Seiflein TA, Lawrence JG: Methionine-to-cysteine recycling in Klebsiella aerogenes. J Bacteriol 2001, 183(1):336-346.
• [180]Delavier-Klutchko C, Flavin M: Enzymatic synthesis and cleavage of cystathionine in fungi and bacteria. J Biol Chem 1965, 240:2537-2549.
• [181]Agren R, Liu L, Shoaie S, Vongsangnak W, Nookaew I, Nielsen J: The RAVEN toolbox and its use for generating a genome-scale metabolic model for Penicillium chrysogenum. PLoS Comput Biol 2013, 9(3):1002980.
• [182]Thorleifsson SG, Thiele I: rBioNet: a COBRA toolbox extension for reconstructing high-quality biochemical networks. Bioinformatics 2011, 27(14):2009-2010.
• [183]Dandekar T, Fieselmann A, Majeed S, Ahmed Z: Software applications toward quantitative metabolic flux analysis and modeling. Brief Bioinform 2014, 15(1):91-107.
• [184]Lakshmanan M, Koh G, Chung BK, Lee DY: Software applications for flux balance analysis. Brief Bioinform 2014, 15(1):108-122.
• [185]Tomar N, De RK: Comparing methods for metabolic network analysis and an application to metabolic engineering. Gene 2013, 521(1):1-14.
• [186]Hamilton JJ, Reed JL: Software platforms to facilitate reconstructing genome-scale metabolic networks. Environ Microbiol 2014, 16(1):49-59.
• [187]Brochado AR, Andrejev S, Maranas CD, Patil KR: Impact of stoichiometry representation on simulation of genotype-phenotype relationships in metabolic networks. PLoS Comput Biol 2012, 8(11):1002758.
• [188]Ebrahim A, Lerman JA, Palsson BØ: COBRApy: COnstraints-Based Reconstruction and Analysis for Python. BMC Syst Biol 2013, 7:74.
• [189]Bochner BR: Global phenotypic characterization of bacteria. FEMS Microbiol Rev 2009, 33(1):191-205.