Cellular metabolism, the integrated interconversion of thousands of metabolic substrates through enzyme-catalysed biochemical reactions, is the most investigated complex intracellular web of molecular interactions. Although the topological organization of individual reactions into metabolic networks is well understood, the principles that govern their global functional use under different growth conditions raise many unanswered questions. By implementing a flux balance analysis of the metabolism of Escherichia coli strain MG1655, here we show that network use is highly uneven. Whereas most metabolic reactions have low fluxes, the overall activity of the metabolism is dominated by several reactions with very high fluxes. E. coli responds to changes in growth conditions by reorganizing the rates of selected fluxes predominantly within this high-flux backbone. This behaviour probably represents a universal feature of metabolic activity in all cells, with potential implications for metabolic engineering.
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Acknowledgements We thank J. Bascompte, S. Cousins, S. Hubbell, R. Naisbit and P. Warren for useful comments. This work was funded by the Swiss National Science Foundation, the Novartis Foundation, and partly by the National Center of Competence in Research ‘Plant Survival’.
Acknowledgements We thank M. Bárász, J. Becker, E. Ravasz, A. Vazquez and S. Wuchty for discussions; and B. Palsson and S. Schuster for comments on the manuscript. Research at Eötvös University was supported by the Hungarian National Research Grant Foundation (OTKA), and work at the University of Notre Dame and at Northwestern University was supported by the US Department of Energy, the NIH and the NSF.