Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor
1 Groningen Bioinformatics Center, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands
2 Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands
3 Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK
4 Integrative and Systems Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
BMC Genomics 2010, 11:202 doi:10.1186/1471-2164-11-202Published: 26 March 2010
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.
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.
Our results show the usefulness of constraint-based modeling for providing a detailed interpretation of time course gene expression data.