STREAM Consortium (Including: Alam, Mohammad T., Merlo, Maria E., Hodgson, D. A. (David A.), Wellington, E. M. H. (Elizabeth M. H.), Takano, Eriko and Breitling, Rainer). (2010) Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor. BMC Genomics, Vol.11 (No.202). p. 202. ISSN 1471-2164

Preview

PDF WRAP_Wellington_Metabolic_modeling.pdf - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader Download (842Kb)

Abstract

Background The transition from exponential to stationary phase in Streptomyces coelicolor is accompanied by a major metabolic switch and results in a strong activation of secondary metabolism. Here we have explored the underlying reorganization of the metabolome by combining computational predictions based on constraint-based modeling and detailed transcriptomics time course observations. Results We reconstructed the stoichiometric matrix of S. coelicolor, including the major antibiotic biosynthesis pathways, and performed flux balance analysis to predict flux changes that occur when the cell switches from biomass to antibiotic production. We defined the model input based on observed fermenter culture data and used a dynamically varying objective function to represent the metabolic switch. The predicted fluxes of many genes show highly significant correlation to the time series of the corresponding gene expression data. Individual mispredictions identify novel links between antibiotic production and primary metabolism. Conclusion Our results show the usefulness of constraint-based modeling for providing a detailed interpretation of time course gene expression data.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Streptomyces coelicolor -- Metabolism, Streptomyces coelicolor -- Genetics, Streptomyces coelicolor -- Mathematical models
Journal or Publication Title:	BMC Genomics
Publisher:	BioMed Central Ltd.
ISSN:	1471-2164
Date:	26 March 2010
Volume:	Vol.11
Number:	No.202
Page Range:	p. 202
Identification Number:	10.1186/1471-2164-11-202
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	European Union (EU), Norges forskningsråd [Norwegian Research Council], Rijksuniversiteit te Groningen [University of Groningen], Nederlandse Organisatie voor Wetenschappelijk Onderzoek [Netherlands Organisation for Scientific Research] (NWO)
Grant number:	GEN2006-27745-E/SYS (ERA-NET), 181840/I30 (Norges forskningsråd)
References:	1. Kolter R, Siegele DA, Tormo A: The stationary phase of the bacterial life cycle. Annu Rev Microbiol 1993, 47:855-874. 2. Roszak DB, Colwell RR: Survival strategies of bacteria in the natural environment. Microbiol Rev 1987, 51(3):365-379. 3. Bentley SD, Chater KF, Cerdeno-Tarraga AM, Challis GL, Thomson NR, James KD, Harris DE, Quail MA, Kieser H, Harper D, et al: Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 2002, 417(6885):141-147. 4. Challis GL, Hopwood DA: Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species. Proc Natl Acad Sci USA 2003, 100(Suppl 2):14555-14561. 5. Borodina I, Siebring J, Zhang J, Smith CP, van Keulen G, Dijkhuizen L, Nielsen J: Antibiotic overproduction in Streptomyces coelicolor A3 2 mediated by phosphofructokinase deletion. J Biol Chem 2008, 283(37):25186-25199. 6. Borodina I, Krabben P, Nielsen J: Genome-scale analysis of Streptomyces coelicolor A3(2) metabolism. Genome Res 2005, 15(6):820-829. 7. Nieselt K, Battke F, Herbig A, Bruheim P, Wentzel A, Jakobsen OM, Sletta H, Alam MT, Merlo ME, Moore J, et al: The dynamic architecture of the metabolic switch in Streptomyces coelicolor. BMC Genomics 2010, 11:10. 8. Price ND, Papin JA, Schilling CH, Palsson BO: Genome-scale microbial in silico models: the constraints-based approach. Trends Biotechnol 2003, 21(4):162-169. 9. Price ND, Reed JL, Palsson BO: Genome-scale models of microbial cells: evaluating the consequences of constraints. Nat Rev Microbiol 2004, 2(11):886-897. 10. Durot M, Bourguignon PY, Schachter V: Genome-scale models of bacterial metabolism: reconstruction and applications. FEMS Microbiol Rev 2009, 33(1):164-190. 11. Lee JM, Gianchandani EP, Papin JA: Flux balance analysis in the era of metabolomics. Brief Bioinform 2006, 7(2):140-150. 12. Covert MW, Schilling CH, Palsson B: Regulation of gene expression in flux balance models of metabolism. J Theor Biol 2001, 213(1):73-88. 13. Lee JM, Gianchandani EP, Eddy JA, Papin JA: Dynamic analysis of integrated signaling, metabolic, and regulatory networks. PLoS Comput Biol 2008, 4(5):e1000086. 14. Melzoch K, de Mattos MJ, Neijssel OM: Production of actinorhodin by Streptomyces coelicolor A3(2) grown in chemostat culture. Biotechnol Bioeng 1997, 54(6):577-582. 15. Wagner A: Energy costs constrain the evolution of gene expression. J Exp Zool B Mol Dev Evol 2007, 308(3):322-324. 16. Wagner A: Energy constraints on the evolution of gene expression. Mol Biol Evol 2005, 22(6):1365-1374. 17. Hojati Z, Milne C, Harvey B, Gordon L, Borg M, Flett F, Wilkinson B, Sidebottom PJ, Rudd BA, Hayes MA, et al: Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor. Chem Biol 2002, 9(11):1175-1187. 18. Cerdeno AM, Bibb MJ, Challis GL: Analysis of the prodiginine biosynthesis gene cluster of Streptomyces coelicolor A3(2): new mechanisms for chain initiation and termination in modular multienzymes. Chem Biol 2001, 8(8):817-829. 19. Apel AK, Sola-Landa A, Rodriguez-Garcia A, Martin JF: Phosphate control of phoA, phoC and phoD gene expression in Streptomyces coelicolor reveals significant differences in binding of PhoP to their promoter regions. Microbiology 2007, 153(Pt 10):3527-3537. 20. Martens JH, Barg H, Warren MJ, Jahn D: Microbial production of vitamin B12. Appl Microbiol Biotechnol 2002, 58(3):275-285. 21. Kim HB, Smith CP, Micklefield J, Mavituna F: Metabolic flux analysis for calcium dependent antibiotic (CDA) production in Streptomyces coelicolor. Metab Eng 2004, 6(4):313-325. 22. Kol S, Merlo ME, Scheltema RA, de Vries M, Vonk RJ, Kikkert NA, Dijkhuizen L, Breitling R, Takano E: Metabolomic characterization of the salt stress response in Streptomyces coelicolor. Appl Environ Microbiol . 23. Akesson M, Forster J, Nielsen J: Integration of gene expression data into genome-scale metabolic models. Metab Eng 2004, 6(4):285-293. 24. Colijn C, Brandes A, Zucker J, Lun DS, Weiner B, Farhat MR, Cheng TY, Moody DB, Murray M, Galagan JE: Interpreting expression data with metabolic flux models: predicting Mycobacterium tuberculosis mycolic acid production. PLoS Comput Biol 2009, 5(8):e1000489. 25. Jamshidi N, Palsson BO: Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets. BMC Syst Biol 2007, 1:26. 26. Reed JL, Vo TD, Schilling CH, Palsson BO: An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR). Genome Biol 2003, 4(9): R54. 27. Oh YK, Palsson BO, Park SM, Schilling CH, Mahadevan R: Genome-scale reconstruction of metabolic network in Bacillus subtilis based on highthroughput phenotyping and gene essentiality data. J Biol Chem 2007, 282(39):28791-28799. 28. Ingraham JL, Maaløe O, Neidhardt FC: Growth of the bacterial cell. Sinauer, Sunderland, MA 1983. 29. Shahab N, Flett F, Oliver SG, Butler PR: Growth rate control of protein and nucleic acid content in Streptomyces coelicolor A3(2) and Escherichia coli B/r. Microbiology 1996, 142(Pt 8):1927-1935. 30. Zuneda MC, Guillenea JJ, Dominguez JB, Prado A, Goni FM: Lipid composition and protoplast-forming capacity of Streptomyces antibioticus. Lipids 1984, 19(3):223-228. 31. Becker SA, Feist AM, Mo ML, Hannum G, Palsson BO, Herrgard MJ: Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox. Nat Protoc 2007, 2(3):727-738.
URI:	http://wrap.warwick.ac.uk/id/eprint/3859

Data sourced from Thomson Reuters' Web of Knowledge

Request changes to a record

Actions (login required)

View Item