Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor

Alam, M.T., Merlo, M.E., Hodgson, D.A., Wellington, E.M.H., Takano, E. and Breitling, R. (2010) Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor. BMC Genomics, 11(202), pp. 1-9. (doi:10.1186/1471-2164-11-202)

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Publisher's 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:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Breitling, Professor Rainer
Authors: Alam, M.T., Merlo, M.E., Hodgson, D.A., Wellington, E.M.H., Takano, E., and Breitling, R.
Subjects:Q Science > Q Science (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:BMC Genomics
Publisher:Biomed Central
ISSN:1471-2164
ISSN (Online):1471-2164
Published Online:26 March 2010
Copyright Holders:Copyright © 2010 The Authors
First Published:First published in BMC Genomics 11(202)
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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