Home LiteratureArticle Details
PMID: 19282977 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Genome-scale reconstruction of Escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.

PLoS computational biology ·Vol. 5 ·No. 3 ·2009-03-00 ·Pages e1000312

Thiele I, Jamshidi N, Fleming RM, Palsson BØ

Abstract

Metabolic network reconstructions represent valuable scaffolds for '-omics' data integration and are used to computationally interrogate network properties. However, they do not explicitly account for the synthesis of macromolecules (i.e., proteins and RNA). Here, we present the first genome-scale, fine-grained reconstruction of Escherichia coli's transcriptional and translational machinery, which produces 423 functional gene products in a sequence-specific manner and accounts for all necessary chemical transformations. Legacy data from over 500 publications and three databases were reviewed, and many pathways were considered, including stable RNA maturation and modification, protein complex formation, and iron-sulfur cluster biogenesis. This reconstruction represents the most comprehensive knowledge base for these important cellular functions in E. coli and is unique in its scope. Furthermore, it was converted into a mathematical model and used to: (1) quantitatively integrate gene expression data as reaction constraints and (2) compute functional network states, which were compared to reported experimental data. For example, the model predicted accurately the ribosome production, without any parameterization. Also, in silico rRNA operon deletion suggested that a high RNA polymerase density on the remaining rRNA operons is needed to reproduce the reported experimental ribosome numbers. Moreover, functional protein modules were determined, and many were found to contain gene products from multiple subsystems, highlighting the functional interaction of these proteins. This genome-scale reconstruction of E. coli's transcriptional and translational machinery presents a milestone in systems biology because it will enable quantitative integration of '-omics' datasets and thus the study of the mechanistic principles underlying the genotype-phenotype relationship.

MeSH Terms
Computer Simulation Databases, Protein Escherichia coli/physiology Escherichia coli Proteins/physiology Gene Expression Regulation, Bacterial/physiology Genome, Bacterial/physiology Models, Biological Protein Modification, Translational/physiology Transcription Factors/physiology Transcription, Genetic/physiology
Chemicals
Escherichia coli Proteins Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Thiele Ines
University of California San Diego, La Jolla, California, United States of America.
Jamshidi Neema
Fleming Ronan M T
Palsson Bernhard Ø
References (62)
62 references, click to expand
  1. 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 PMID: 17593909
  2. Depletion of functional ribosomal RNA operons in Escherichia coli causes increased expression of the remaining intact copies.
    EMBO J. 1993 Nov;12(11):4305-15 PMID: 8223440
  3. Global analysis of mRNA decay and abundance in Escherichia coli at single-gene resolution using two-color fluorescent DNA microarrays.
    Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9697-702 PMID: 12119387
  4. Metabolite coupling in genome-scale metabolic networks.
    BMC Bioinformatics. 2006 Mar 06;7:111 PMID: 16519800
  5. Metabolic modelling of microbes: the flux-balance approach.
    Environ Microbiol. 2002 Mar;4(3):133-40 PMID: 12000313
  6. Genome-scale metabolic network analysis of the opportunistic pathogen Pseudomonas aeruginosa PAO1.
    J Bacteriol. 2008 Apr;190(8):2790-803 PMID: 18192387
  7. Formulating genome-scale kinetic models in the post-genome era.
    Mol Syst Biol. 2008;4:171 PMID: 18319723
  8. Large-scale identification of protein-protein interaction of Escherichia coli K-12.
    Genome Res. 2006 May;16(5):686-91 PMID: 16606699
  9. Escherichia coli K-12: a cooperatively developed annotation snapshot--2005.
    Nucleic Acids Res. 2006 Jan 05;34(1):1-9 PMID: 16397293
  10. Translation initiation factor IF1 is essential for cell viability in Escherichia coli.
    J Bacteriol. 1994 Jan;176(1):198-205 PMID: 8282696
  11. Matrix formalism to describe functional states of transcriptional regulatory systems.
    PLoS Comput Biol. 2006 Aug 11;2(8):e101 PMID: 16895435
  12. An algorithmic framework for genome-wide modeling and analysis of translation networks.
    Biophys J. 2006 Feb 15;90(4):1136-46 PMID: 16299083
  13. A model for protein translation: polysome self-organization leads to maximum protein synthesis rates.
    Biophys J. 2007 Feb 1;92(3):717-30 PMID: 17098800
  14. Reconstruction of biochemical networks in microorganisms.
    Nat Rev Microbiol. 2009 Feb;7(2):129-43 PMID: 19116616
  15. Genome-scale models of microbial cells: evaluating the consequences of constraints.
    Nat Rev Microbiol. 2004 Nov;2(11):886-97 PMID: 15494745
  16. Insights into the relation between mRNA and protein expression patterns: I. Theoretical considerations.
    Biotechnol Bioeng. 2003 Dec 30;84(7):822-33 PMID: 14708123
  17. On protein synthesis.
    Symp Soc Exp Biol. 1958;12:138-63 PMID: 13580867
  18. Global organization of metabolic fluxes in the bacterium Escherichia coli.
    Nature. 2004 Feb 26;427(6977):839-43 PMID: 14985762
  19. Construction and initial characterization of Escherichia coli strains with few or no intact chromosomal rRNA operons.
    J Bacteriol. 1999 Jun;181(12):3803-9 PMID: 10368156
  20. Genome-scale reconstruction and analysis of the Pseudomonas putida KT2440 metabolic network facilitates applications in biotechnology.
    PLoS Comput Biol. 2008 Oct;4(10):e1000210 PMID: 18974823
  21. Global reconstruction of the human metabolic network based on genomic and bibliomic data.
    Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1777-82 PMID: 17267599
  22. Rapid responses of ribosomal RNA synthesis to nutrient shifts.
    Biotechnol Bioeng. 2007 Aug 1;97(5):1230-45 PMID: 17216653
  23. A coarse-grained biophysical model of E. coli and its application to perturbation of the rRNA operon copy number.
    PLoS Comput Biol. 2008 May 02;4(4):e1000038 PMID: 18437222
  24. Flux coupling analysis of genome-scale metabolic network reconstructions.
    Genome Res. 2004 Feb;14(2):301-12 PMID: 14718379
  25. Biosynthesis of the pyrrolopyrimidine nucleoside antibiotic, toyocamycin. VII. Origin of the pyrrole carbons and the cyano carbon.
    J Biol Chem. 1970 Sep 10;245(17):4365-71 PMID: 5498424
  26. Increased rrn gene dosage causes intermittent transcription of rRNA in Escherichia coli.
    J Bacteriol. 1999 Jul;181(14):4170-5 PMID: 10400572
  27. Candidate metabolic network states in human mitochondria. Impact of diabetes, ischemia, and diet.
    J Biol Chem. 2005 Mar 25;280(12):11683-95 PMID: 15572364
  28. A computational framework for the topological analysis and targeted disruption of signal transduction networks.
    Biophys J. 2006 Jul 1;91(1):382-98 PMID: 16617070
  29. The complete genome sequence of Escherichia coli K-12.
    Science. 1997 Sep 5;277(5331):1453-62 PMID: 9278503
  30. Metabolic gene-deletion strains of Escherichia coli evolve to computationally predicted growth phenotypes.
    Nat Genet. 2004 Oct;36(10):1056-8 PMID: 15448692
  31. Cell biology. Alliance launched to model E. coli.
    Science. 2002 Aug 30;297(5586):1459-60 PMID: 12202792
  32. Metabolic engineering of Escherichia coli for the production of L-valine based on transcriptome analysis and in silico gene knockout simulation.
    Proc Natl Acad Sci U S A. 2007 May 8;104(19):7797-802 PMID: 17463081
  33. Towards multidimensional genome annotation.
    Nat Rev Genet. 2006 Feb;7(2):130-41 PMID: 16418748
  34. The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities.
    Proc Natl Acad Sci U S A. 2000 May 9;97(10):5528-33 PMID: 10805808
  35. Systems approach to refining genome annotation.
    Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17480-4 PMID: 17088549
  36. Integrating metabolic, transcriptional regulatory and signal transduction models in Escherichia coli.
    Bioinformatics. 2008 Sep 15;24(18):2044-50 PMID: 18621757
  37. Dynamic analysis of integrated signaling, metabolic, and regulatory networks.
    PLoS Comput Biol. 2008 May 23;4(5):e1000086 PMID: 18483615
  38. A genome-scale metabolic reconstruction of Pseudomonas putida KT2440: iJN746 as a cell factory.
    BMC Syst Biol. 2008 Sep 16;2:79 PMID: 18793442
  39. Interaction network containing conserved and essential protein complexes in Escherichia coli.
    Nature. 2005 Feb 3;433(7025):531-7 PMID: 15690043
  40. Genome-scale microbial in silico models: the constraints-based approach.
    Trends Biotechnol. 2003 Apr;21(4):162-9 PMID: 12679064
  41. rRNA operon multiplicity in Escherichia coli and the physiological implications of rrn inactivation.
    J Bacteriol. 1995 Jul;177(14):4152-6 PMID: 7608093
  42. Compilation of tRNA sequences and sequences of tRNA genes.
    Nucleic Acids Res. 2005 Jan 1;33(Database issue):D139-40 PMID: 15608164
  43. The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli.
    Nat Biotechnol. 2008 Jun;26(6):659-67 PMID: 18536691
  44. Systems analysis of metabolism in the pathogenic trypanosomatid Leishmania major.
    Mol Syst Biol. 2008;4:177 PMID: 18364711
  45. Life history implications of rRNA gene copy number in Escherichia coli.
    Appl Environ Microbiol. 2004 Nov;70(11):6670-7 PMID: 15528533
  46. Genetics of bacterial ribosomes.
    Annu Rev Genet. 1977;11:297-347 PMID: 339818
  47. Proteome-wide analysis of chaperonin-dependent protein folding in Escherichia coli.
    Cell. 2005 Jul 29;122(2):209-20 PMID: 16051146
  48. Reconstruction and validation of Saccharomyces cerevisiae iND750, a fully compartmentalized genome-scale metabolic model.
    Genome Res. 2004 Jul;14(7):1298-309 PMID: 15197165
  49. Expanded metabolic reconstruction of Helicobacter pylori (iIT341 GSM/GPR): an in silico genome-scale characterization of single- and double-deletion mutants.
    J Bacteriol. 2005 Aug;187(16):5818-30 PMID: 16077130
  50. The CyberCell Database (CCDB): a comprehensive, self-updating, relational database to coordinate and facilitate in silico modeling of Escherichia coli.
    Nucleic Acids Res. 2004 Jan 1;32(Database issue):D293-5 PMID: 14681416
  51. Transcription regulation by initiating NTP concentration: rRNA synthesis in bacteria.
    Science. 1997 Dec 19;278(5346):2092-7 PMID: 9405339
  52. The biosynthesis of the 7-deazaadenine ribonucleoside, tubercidin, by Streptomyces tubercidicus.
    J Biol Chem. 1967 Jun 25;242(12):2872-6 PMID: 6027250
  53. Regulation of the synthesis of ribosomes and ribosomal components.
    Annu Rev Biochem. 1984;53:75-117 PMID: 6206783
  54. Sequence-based analysis of metabolic demands for protein synthesis in prokaryotes.
    J Theor Biol. 2003 Jan 7;220(1):1-18 PMID: 12453446
  55. Trigger Factor and DnaK possess overlapping substrate pools and binding specificities.
    Mol Microbiol. 2003 Mar;47(5):1317-28 PMID: 12603737
  56. The effects of alternate optimal solutions in constraint-based genome-scale metabolic models.
    Metab Eng. 2003 Oct;5(4):264-76 PMID: 14642354
  57. The KEGG resource for deciphering the genome.
    Nucleic Acids Res. 2004 Jan 1;32(Database issue):D277-80 PMID: 14681412
  58. Large-scale evaluation of in silico gene deletions in Saccharomyces cerevisiae.
    OMICS. 2003 Summer;7(2):193-202 PMID: 14506848
  59. Reconstruction of cellular signalling networks and analysis of their properties.
    Nat Rev Mol Cell Biol. 2005 Feb;6(2):99-111 PMID: 15654321
  60. Regulation of ribosome biosynthesis in Escherichia coli and Saccharomyces cerevisiae: diversity and common principles.
    J Bacteriol. 1999 Nov;181(22):6857-64 PMID: 10559149
  61. Integrating high-throughput and computational data elucidates bacterial networks.
    Nature. 2004 May 6;429(6987):92-6 PMID: 15129285
  62. Metabolic functions of duplicate genes in Saccharomyces cerevisiae.
    Genome Res. 2005 Oct;15(10):1421-30 PMID: 16204195
Article Info
Journal
PLoS computational biology
Abbr.
PLoS Comput Biol
ISSN
1553-7358
DOI
10.1371/journal.pcbi.1000312
Published
2009-03-00
Epub
2009-00-13
Pages
e1000312
Language
English
Region
United States
NLM ID
101238922
PMCID
PMC2648898
Subset
IM
Grants
PHS HHS · R0157089 · United States
External Links
PubMed source DOI: 10.1371/journal.pcbi.1000312 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2