A significant goal in the post-genome era is to relate the annotated genome sequence to the physiological functions of a cell. Working from the annotated genome sequence, as well as biochemical and physiological information, it is possible to reconstruct complete metabolic networks. Furthermore, computational methods have been developed to interpret and predict the optimal performance of a metabolic network under a range of growth conditions. We have tested the hypothesis that Escherichia coli uses its metabolism to grow at a maximal rate using the E. coli MG1655 metabolic reconstruction. Based on this hypothesis, we formulated experiments that describe the quantitative relationship between a primary carbon source (acetate or succinate) uptake rate, oxygen uptake rate, and maximal cellular growth rate. We found that the experimental data were consistent with the stated hypothesis, namely that the E. coli metabolic network is optimized to maximize growth under the experimental conditions considered. This study thus demonstrates how the combination of in silico and experimental biology can be used to obtain a quantitative genotype–phenotype relationship for metabolism in bacterial cells.
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This work was funded by the NIH (GM57089) and the NSF (MCB 98-73384 and BES 98-14092). We would like to thank Christophe Schilling and George M. Church for insightful discussions during the preparation of this manuscript, and Markus Covert and Iman Famili for technical assistance.
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Edwards, J., Ibarra, R. & Palsson, B. In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data. Nat Biotechnol 19, 125–130 (2001). https://doi.org/10.1038/84379
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