STREAM Consortium (Including: Alam, Mohammad T., Merlo, Maria E., Hodgson, D. A., Wellington, E. 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. doi:10.1186/1471-2164-11-202 ISSN 1471-2164.

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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, Engineering and Medicine > 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
Official Date:	26 March 2010
Dates:	Date Event 26 March 2010 Published
Volume:	Vol.11
Number:	No.202
Page Range:	p. 202
DOI:	10.1186/1471-2164-11-202
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
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)

Data sourced from Thomson Reuters' Web of Knowledge

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