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Global organization of metabolic fluxes in the bacterium Escherichia coli


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 understood1,2,3,4, the principles that govern their global functional use under different growth conditions raise many unanswered questions5,6,7. By implementing a flux balance analysis8,9,10,11,12 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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Figure 1: Characterizing the overall flux organization of the E. coli metabolic network.
Figure 2: Characterizing the local inhomogeneity of the metabolic flux distribution.
Figure 3: High-flux backbone for FBA-optimized metabolic network of E. coli on a glutamate-rich substrate (see Supplementary Fig. S12b for succinate-rich substrate).
Figure 4: Effect of growth conditions on individual fluxes.

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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.

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Correspondence to A.-L. Barabási.

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Almaas, E., Kovács, B., Vicsek, T. et al. Global organization of metabolic fluxes in the bacterium Escherichia coli. Nature 427, 839–843 (2004).

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