title: Basic and applied uses of genome-scale metabolic network reconstructions of Escherichia coli.
abstract: The genome-scale model (GEM) of metabolism in the bacterium Escherichia coli K-12 has been in development for over a decade and is now in wide use. GEM-enabled studies of E. coli have been primarily focused on six applications: (1) metabolic engineering, (2) model-driven discovery, (3) prediction of cellular phenotypes, (4) analysis of biological network properties, (5) studies of evolutionary processes, and (6) models of interspecies interactions. In this review, we provide an overview of these applications along with a critical assessment of their successes and limitations, and a perspective on likely future developments in the field. Taken together, the studies performed over the past decade have established a genome-scale mechanistic understanding of genotype-phenotype relationships in E. coli metabolism that forms the basis for similar efforts for other microbial species. Future challenges include the expansion of GEMs by integrating additional cellular processes beyond metabolism, the identification of key constraints based on emerging data types, and the development of computational methods able to handle such large-scale network models with sufficient accuracy.
authors: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Douglas
authors: D
authors: McCloskey
authors: Bernhard Ø
authors: BØ
authors: Palsson
authors: Adam M
authors: AM
authors: Feist
mesh_terms: D005075:Biological Evolution; D003198:Computer Simulation; D048168:Escherichia coli K12 / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D056726:Genetic Association Studies; D016680:Genome, Bacterial; D005838:Genotype; D060847:Metabolic Engineering / Q000379:methods; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008957:Models, Genetic; D010641:Phenotype
chemical_list: D029968:Escherichia coli Proteins
references: Biotechnol Bioeng. 1997 Nov 20;56(4):398-421
references: 18642243
references: Biotechnol Bioeng. 2005 Sep 5;91(5):643-8
references: 15962337
references: Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4645-52
references: 20615995
references: Biotechnol Adv. 2012 Sep-Oct;30(5):979-88
references: 21846501
references: Nat Rev Microbiol. 2009 Feb;7(2):129-43
references: 19116616
references: J Theor Biol. 2005 Dec 21;237(4):401-11
references: 15975601
references: J Biol Chem. 2009 Oct 23;284(43):29480-8
references: 19690172
references: Bioinformatics. 2005 Sep 1;21 Suppl 2:ii222-3
references: 16204108
references: BMC Bioinformatics. 2012 Jan 10;13:6
references: 22233419
references: Metab Eng. 2010 Mar;12(2):105-11
references: 19481614
references: Nat Rev Microbiol. 2004 Nov;2(11):886-97
references: 15494745
references: Nat Protoc. 2010 Jan;5(1):93-121
references: 20057383
references: Nature. 2004 Feb 26;427(6977):839-43
references: 14985762
references: Nat Chem Biol. 2012 May 17;8(6):536-46
references: 22596205
references: Mol Syst Biol. 2008;4:168
references: 18277384
references: Science. 2012 May 4;336(6081):601-4
references: 22556256
references: Nat Genet. 2006 Dec;38(12):1406-12
references: 17086184
references: BMC Syst Biol. 2009 Dec 30;3:121
references: 20042079
references: Bioinformatics. 2010 Jun 15;26(12):i255-60
references: 20529914
references: PLoS One. 2012;7(9):e45635
references: 23029152
references: Science. 1997 Sep 5;277(5331):1453-62
references: 9278503
references: Nat Genet. 2005 Dec;37(12):1372-5
references: 16311593
references: PLoS Comput Biol. 2008 May 16;4(5):e1000082
references: 18483554
references: Biotechnol Prog. 2010 Jan-Feb;26(1):1-10
references: 19785030
references: Nat Genet. 2004 Oct;36(10):1056-8
references: 15448692
references: BMC Syst Biol. 2011 Oct 18;5:167
references: 22008379
references: Proc Natl Acad Sci U S A. 2000 May 9;97(10):5528-33
references: 10805808
references: Biophys Chem. 2009 Dec;145(2-3):47-56
references: 19783351
references: Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19103-8
references: 16357206
references: J Theor Biol. 2000 Apr 7;203(3):229-48
references: 10716907
references: BMC Syst Biol. 2011 Nov 01;5:182
references: 22044664
references: Nature. 2002 Nov 14;420(6912):186-9
references: 12432395
references: Mol Syst Biol. 2009;5:301
references: 19690570
references: Gene. 2011 Jul 1;480(1-2):1-9
references: 21402131
references: BMC Syst Biol. 2011 Mar 15;5:40
references: 21406074
references: FEBS Lett. 2009 Dec 17;583(24):3900-4
references: 19769971
references: Mol Syst Biol. 2007;3:121
references: 17593909
references: Biotechnol Bioeng. 2011 Feb;108(2):376-85
references: 20882517
references: Biotechnol J. 2011 Sep;6(9):1052-63
references: 21845736
references: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17480-4
references: 17088549
references: Mol Syst Biol. 2011 Jun 21;7:500
references: 21694717
references: BMC Syst Biol. 2010 Apr 28;4:53
references: 20426856
references: Nat Biotechnol. 2005 May;23(5):612-6
references: 15821729
references: Science. 2010 Jul 30;329(5991):533-8
references: 20671182
references: BMC Bioinformatics. 2006 Nov 23;7:512
references: 17123434
references: Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12663-8
references: 17652176
references: Biophys J. 2007 Mar 15;92(6):1846-57
references: 17208985
references: Nat Chem Biol. 2011 May 22;7(7):445-52
references: 21602812
references: Appl Environ Microbiol. 2010 Oct;76(19):6529-40
references: 20709841
references: Anal Chem. 2009 Mar 15;81(6):2135-43
references: 19236023
references: Nature. 2006 Mar 30;440(7084):667-70
references: 16572170
references: BMC Bioinformatics. 2005 Dec 23;6:308
references: 16375763
references: BMC Syst Biol. 2008 Feb 29;2:21
references: 18312613
references: Biosystems. 2011 Jan;103(1):57-66
references: 20888889
references: Metab Eng. 2010 Mar;12(2):96-104
references: 19628048
references: BMC Syst Biol. 2011 Aug 24;5:135
references: 21864340
references: BMC Syst Biol. 2008 Jan 23;2:7
references: 18215292
references: Genome Biol. 2010;11(4):R43
references: 20398381
references: J Biol Chem. 2011 Jul 1;286(26):23150-9
references: 21550976
references: Mol Syst Biol. 2011 Mar 29;7:479
references: 21451589
references: Bioinformatics. 2012 Sep 15;28(18):i502-i508
references: 22962473
references: Genome Biol. 2009 Feb 12;10(2):R19
references: 19216750
references: BMC Bioinformatics. 2007 Jun 20;8:212
references: 17584497
references: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
references: 10829079
references: Genome Biol. 2009;10(10):R118
references: 19849850
references: Nat Biotechnol. 2008 Jun;26(6):659-67
references: 18536691
references: Proc Natl Acad Sci U S A. 2005 May 24;102(21):7695-700
references: 15897462
references: PLoS One. 2011;6(7):e22295
references: 21779409
references: J Bacteriol. 2006 Dec;188(23):8259-71
references: 17012394
references: Mol Biosyst. 2011 Nov;7(11):3056-64
references: 21881679
references: Appl Environ Microbiol. 2009 Sep;75(18):5831-9
references: 19633125
references: Biotechnol Bioeng. 1993 Jun 5;42(1):59-73
references: 18609648
references: Biotechnol Bioeng. 2011 Jun;108(6):1372-82
references: 21328316
references: Mol Syst Biol. 2010 Jul;6:390
references: 20664636
references: PLoS Comput Biol. 2010 Oct 28;6(10):e1000970
references: 21060853
references: Nat Rev Microbiol. 2012 Feb 27;10(4):291-305
references: 22367118
references: J Bacteriol. 2007 Nov;189(22):8073-8
references: 17873044
references: Mol Syst Biol. 2011 Oct 11;7:535
references: 21988831
references: PLoS Comput Biol. 2009 Mar;5(3):e1000312
references: 19282977
references: BMC Bioinformatics. 2008 Apr 16;9:199
references: 18416814
references: Appl Environ Microbiol. 1994 Oct;60(10):3724-31
references: 7986045
references: Mol Syst Biol. 2007;3:149
references: 18059444
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D770-5
references: 22064852
references: Mol Syst Biol. 2011 Jul 05;7:509
references: 21734648
references: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15112-7
references: 12415116
references: J R Soc Interface. 2010 Jul 6;7(48):1015-24
references: 20022895
references: Mol Syst Biol. 2007;3:101
references: 17437026
references: BMC Syst Biol. 2008 Jul 24;2:67
references: 18652654
references: Appl Environ Microbiol. 2010 Jul;76(13):4158-68
references: 20435762
references: Biophys J. 2007 Mar 1;92(5):1792-805
references: 17172310
references: Nat Biotechnol. 2010 Sep;28(9):977-82
references: 20802497
references: Mol Cell Proteomics. 2008 Feb;7(2):299-307
references: 17938405
references: Metab Eng. 2011 Sep;13(5):578-87
references: 21763447
references: Mol Syst Biol. 2011 Jul 19;7:515
references: 21772263
references: Nat Rev Microbiol. 2012 Mar 27;10(5):366-72
references: 22450377
references: J R Soc Interface. 2012 Jun 7;9(71):1168-76
references: 22130553
references: Bioinformatics. 2009 Dec 1;25(23):3158-65
references: 19793869
references: Metab Eng. 2011 Jan;13(1):38-48
references: 21129495
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D480-4
references: 18077471
references: Genome Biol. 2003;4(9):R54
references: 12952533
references: Front Plant Sci. 2011 Aug 11;2:38
references: 22645533
references: J Theor Biol. 2003 Jan 7;220(1):1-18
references: 12453446
references: PLoS Comput Biol. 2008 Dec;4(12):e1000236
references: 19057639
references: Nat Biotechnol. 2010 Mar;28(3):245-8
references: 20212490
references: Biotechnol Bioeng. 1990 Mar 25;35(7):732-8
references: 18592570
references: Mol Syst Biol. 2010 Sep 7;6:407
references: 20823845
references: Mol Syst Biol. 2010 May 11;6:364
references: 20461071
references: Mol Syst Biol. 2009;5:320
references: 19888215
references: J Biotechnol. 2007 May 10;129(4):696-705
references: 17408794
references: Metab Eng. 2012 May;14(3):270-80
references: 22629572
references: Biophys J. 2008 Aug;95(3):1487-99
references: 18645197
references: Science. 2006 Dec 8;314(5805):1601-3
references: 17158328
references: J Biol Chem. 2010 Jun 4;285(23):17498-506
references: 20299454
references: Biotechnol Prog. 2009 Jan-Feb;25(1):61-7
references: 19224555
references: J Theor Biol. 1993 Dec 21;165(4):477-502
references: 21322280
references: Mol Syst Biol. 2009;5:306
references: 19756045
references: BMC Bioinformatics. 2007 Sep 27;8(1):363
references: 17897474
references: Biotechnol Bioeng. 2003 Dec 20;84(6):647-57
references: 14595777
references: Mol Biol Rep. 2002;29(1-2):233-6
references: 12241063
references: PLoS Genet. 2010 Nov 04;6(11):e1001186
references: 21079674
references: Nature. 2004 May 6;429(6987):92-6
references: 15129285
references: Biotechnol Bioeng. 2010 Jan 1;105(1):161-71
references: 19937727
references: Mol Syst Biol. 2007;3:119
references: 17625511
references: Cell Host Microbe. 2009 Feb 19;5(2):114-22
references: 19218083
references: Nat Methods. 2009 May;6(5):377-82
references: 19349980
references: Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1082-7
references: 20080587
references: Trends Biotechnol. 1999 Feb;17(2):53-60
references: 10087604
references: PLoS Comput Biol. 2010 Nov 18;6(11):e1001002
references: 21124952
references: PLoS Comput Biol. 2006 Jul 7;2(7):e72
references: 16839195
references: Brief Funct Genomics. 2011 Sep;10(5):266-79
references: 21903724