Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor
© Alam et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
We are very grateful to the STREAM consortium (funded by ERA-NET SySMO [GEN2006-27745-E/SYS]: (P-UK-01-11-3i) and the Research Council of Norway [project no. 181840/I30]) for providing the expression data prior to publication. The STREAM consortium is an international project funded by a SysMO grant of the ERASysBio framework http://www.erasysbio.net studying "Global metabolic switching in Streptomyces coelicolor". Members of the consortium include Florian Battke, Sven Even Borgos, Per Bruheim, Nigel Burroughs, Gregory Challis, Lubbert Dijkhuizen, Trond E Ellingsen, William Gaze, Alexander Herbig, Sunniva Hoel, Øyvind Jakobsen, Ritsert C. Jansen, Brent Kiernan, Preben Krabben, Roxane Legaie, Juan Francisco Martín, Jay Moore, Kay Nieselt, Walid Omara, David Rand, Jens Reuther, Antonio Rodríguez-García, Håvard Sletta, Maggie Smith, Louise Thomas, Alexander Wentzel, David Wild, Wolfgang Wohlleben, Arouna Woukeu, Anders Øverby, and the authors https://www.wsbc.warwick.ac.uk/groups/sysmopublic/. MEM was funded by a 4 × 4 Ubbo Emmius scholarship and ET by a Rosalind Franklin Fellowship, both from the University of Groningen. RB is supported by an NWO-Vidi fellowship.
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Vol. 11, article 202
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