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Metabolic switching in Streptomyces coelicolor Timeseries 1

ABSTRACT: Background: During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples. Results: Surprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2 hours, and changes in antibiotic biosynthesis genes are delayed relative to the metabolic rearrangements. Furthermore, global variation in morphogenesis genes indicates an involvement of cell differentiation pathways in the decision phase leading up to the commitment to antibiotic biosynthesis. Conclusions: Our study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological setting. Keywords: time course

ORGANISM(S): Streptomyces coelicolor Streptomyces coelicolor A3(2)

PROVIDER: GSE18489 | GEO | 2009/12/14

SECONDARY ACCESSION(S): PRJNA120235

REPOSITORIES: GEO

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Project description:Alam2010 - Genome-scale metabolic network of Streptomyces coelicolor This model is described in the article: Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor. Alam MT, Merlo ME, STREAM Consortium, Hodgson DA, Wellington EM, Takano E, Breitling R. BMC Genomics 2010; 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. This model is hosted on BioModels Database and identified by: MODEL1507180005. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Metabolic switching in Streptomyces coelicolor Timeseries 1

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