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Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor
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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
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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: |
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| 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 | ||||
| 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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