title: Dissecting the energy metabolism in Mycoplasma pneumoniae through genome-scale metabolic modeling.
abstract: Mycoplasma pneumoniae, a threatening pathogen with a minimal genome, is a model organism for bacterial systems biology for which substantial experimental information is available. With the goal of understanding the complex interactions underlying its metabolism, we analyzed and characterized the metabolic network of M. pneumoniae in great detail, integrating data from different omics analyses under a range of conditions into a constraint-based model backbone. Iterating model predictions, hypothesis generation, experimental testing, and model refinement, we accurately curated the network and quantitatively explored the energy metabolism. In contrast to other bacteria, M. pneumoniae uses most of its energy for maintenance tasks instead of growth. We show that in highly linear networks the prediction of flux distributions for different growth times allows analysis of time-dependent changes, albeit using a static model. By performing an in silico knock-out study as well as analyzing flux distributions in single and double mutant phenotypes, we demonstrated that the model accurately represents the metabolism of M. pneumoniae. The experimentally validated model provides a solid basis for understanding its metabolic regulatory mechanisms.
authors.affiliation: EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Barcelona, Spain.
authors.forename: Judith A H
authors.initials: JA
authors.lastname: Wodke
authors.forename: Jacek
authors.initials: J
authors.lastname: Puchałka
authors.forename: Maria
authors.initials: M
authors.lastname: Lluch-Senar
authors.forename: Josep
authors.initials: J
authors.lastname: Marcos
authors.forename: Eva
authors.initials: E
authors.lastname: Yus
authors.forename: Miguel
authors.initials: M
authors.lastname: Godinho
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gutiérrez-Gallego
authors.forename: Vitor A P Martins
authors.initials: VA
authors.lastname: dos Santos
authors.forename: Luis
authors.initials: L
authors.lastname: Serrano
authors.forename: Edda
authors.initials: E
authors.lastname: Klipp
authors.forename: Tobias
authors.initials: T
authors.lastname: Maier
mesh_terms: D003198:Computer Simulation; D004734:Energy Metabolism / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008954:Models, Biological; D009154:Mutation; D009177:Mycoplasma pneumoniae / Q000235:genetics* / Q000378:metabolism*
references.citation: Cell. 2012 Jul 20;150(2):389-401
references.pmid: 22817898
references.citation: Biochem J. 1986 Sep 15;238(3):781-6
references.pmid: 3800960
references.citation: Bioinformatics. 2011 Jul 15;27(14):2009-10
references.pmid: 21596791
references.citation: Nucleic Acids Res. 1996 Nov 15;24(22):4420-49
references.pmid: 8948633
references.citation: J Biol Chem. 2006 Sep 8;281(36):26253-9
references.pmid: 16857667
references.citation: J Gen Microbiol. 1963 Dec;33:477-87
references.pmid: 14118039
references.citation: Nucleic Acids Res. 2000 Sep 1;28(17):3278-88
references.pmid: 10954595
references.citation: Crit Rev Microbiol. 1997;23(4):269-354
references.pmid: 9439886
references.citation: Infect Immun. 1970 Sep;2(3):326-39
references.pmid: 16557840
references.citation: Nat Rev Microbiol. 2009 Feb;7(2):129-43
references.pmid: 19116616
references.citation: Nat Genet. 2011 May 29;43(7):656-62
references.pmid: 21623372
references.citation: Nat Rev Microbiol. 2004 Nov;2(11):886-97
references.pmid: 15494745
references.citation: Nat Protoc. 2011 Aug 04;6(9):1290-307
references.pmid: 21886097
references.citation: Science. 2012 Mar 2;335(6072):1099-103
references.pmid: 22383848
references.citation: PLoS Comput Biol. 2008 Oct;4(10):e1000210
references.pmid: 18974823
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1777-82
references.pmid: 17267599
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):425-30
references.pmid: 16407165
references.citation: Biochem Soc Symp. 2001;(68):45-68
references.pmid: 11573347
references.citation: J Theor Biol. 2001 Nov 7;213(1):73-88
references.pmid: 11708855
references.citation: Science. 2012 May 4;336(6081):601-4
references.pmid: 22556256
references.citation: Proc R Soc Lond B Biol Sci. 1965 Oct 12;163(991):224-31
references.pmid: 4378482
references.citation: J Struct Biol. 2006 Nov;156(2):342-54
references.pmid: 16875842
references.citation: BMC Bioinformatics. 2000;1:1
references.pmid: 11001586
references.citation: Mol Syst Biol. 2011 Jul 19;7:511
references.pmid: 21772259
references.citation: Science. 2009 Nov 27;326(5957):1235-40
references.pmid: 19965468
references.citation: Science. 2009 Nov 27;326(5957):1268-71
references.pmid: 19965477
references.citation: Nat Rev Genet. 2006 Feb;7(2):130-41
references.pmid: 16418748
references.citation: Mol Syst Biol. 2006;2:2006.0008
references.pmid: 16738554
references.citation: Biochim Biophys Acta. 1980 May 27;604(1):65-90
references.pmid: 6992872
references.citation: Biophys Chem. 2009 Dec;145(2-3):47-56
references.pmid: 19783351
references.citation: Mol Syst Biol. 2007;3:121
references.pmid: 17593909
references.citation: Science. 1969 Apr 25;164(3878):433-4
references.pmid: 5777213
references.citation: Bioinformatics. 1999 Jul-Aug;15(7-8):536-43
references.pmid: 10487861
references.citation: Science. 2001 Dec 14;294(5550):2364-8
references.pmid: 11743205
references.citation: FEMS Microbiol Rev. 2005 Aug;29(3):531-54
references.pmid: 15939503
references.citation: Environ Microbiol. 2002 Mar;4(3):133-40
references.pmid: 12000313
references.citation: Science. 2001 Feb 9;291(5506):1001-4
references.pmid: 11232561
references.citation: J Theor Biol. 1992 Mar 21;155(2):215-42
references.pmid: 1453698
references.citation: J Bacteriol. 2006 Dec;188(23):8259-71
references.pmid: 17012394
references.citation: J Bacteriol. 2004 Jul;186(13):4254-61
references.pmid: 15205428
references.citation: J Bacteriol. 2008 Apr;190(8):2790-803
references.pmid: 18192387
references.citation: Mol Syst Biol. 2011 Oct 11;7:535
references.pmid: 21988831
references.citation: J Theor Biol. 1992 Mar 21;155(2):201-14
references.pmid: 1453697
references.citation: Proc Natl Acad Sci U S A. 1962 Jan 15;48:41-9
references.pmid: 13878126
references.citation: Appl Environ Microbiol. 1994 Oct;60(10):3724-31
references.pmid: 7986045
references.citation: Science. 2004 Feb 6;303(5659):808-13
references.pmid: 14764870
references.citation: J Bacteriol. 2009 Feb;191(3):747-53
references.pmid: 19028882
references.citation: Mol Syst Biol. 2012 Feb 28;8:571
references.pmid: 22373819
references.citation: J Theor Biol. 2003 Apr 7;221(3):309-25
references.pmid: 12642111
references.citation: Sci Rep. 2012;2:621
references.pmid: 22934134
references.citation: Nat Rev Microbiol. 2011 Aug 12;9(9):658-69
references.pmid: 21836626
references.citation: Nat Biotechnol. 2010 Sep;28(9):977-82
references.pmid: 20802497
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: Curr Opin Biotechnol. 2003 Oct;14(5):491-6
references.pmid: 14580578
references.citation: Nat Protoc. 2011 Sep 08;6(10):1483-99
references.pmid: 21959233
references.citation: Clin Microbiol Rev. 2004 Oct;17(4):697-728, table of contents
references.pmid: 15489344
references.citation: J Bacteriol. 2003 May;185(9):2692-9
references.pmid: 12700248
references.citation: J Biol Chem. 1985 Jan 10;260(1):72-6
references.pmid: 2856922
references.citation: J Gen Microbiol. 1988 Mar;134(3):791-800
references.pmid: 3141576
references.citation: Genetics. 1998 Apr;148(4):1667-86
references.pmid: 9560386
references.citation: Science. 2012 Mar 2;335(6072):1103-6
references.pmid: 22383849
references.citation: Mol Syst Biol. 2009;5:320
references.pmid: 19888215
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):27-30
references.pmid: 10592173
references.citation: Bioinformatics. 2011 Jan 1;27(1):142-3
references.pmid: 21115436
references.citation: BMC Syst Biol. 2011 Oct 01;5:155
references.pmid: 21962087
references.citation: Nat Biotechnol. 2005 Aug;23(8):961-6
references.pmid: 16082367
references.citation: J Clin Microbiol. 1991 Jun;29(6):1114-24
references.pmid: 1864927
references.citation: PLoS Comput Biol. 2009 Feb;5(2):e1000285
references.pmid: 19214212
references.citation: J Biol Chem. 1995 May 19;270(20):11803-5
references.pmid: 7744829
references.citation: Nature. 2002 Nov 14;420(6912):206-10
references.pmid: 12432404
references.citation: PLoS Pathog. 2011 Sep;7(9):e1002263
references.pmid: 21966272
references.citation: Science. 2009 Nov 27;326(5957):1263-8
references.pmid: 19965476
references.citation: Int J Med Microbiol. 2007 Feb;297(1):37-44
references.pmid: 17223385
references.citation: Biochem J. 1998 Mar 1;330 ( Pt 2):853-60
references.pmid: 9480901