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Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor

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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. ISSN 1471-2164

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Official URL: http://dx.doi.org/10.1186/1471-2164-11-202

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

Official Date:

26 March 2010

Dates:

Date	Event
26 March 2010	Published

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)

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