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FEBS J. 2012 Sep;279(18):3374-85. doi: 10.1111/j.1742-4658.2012.08719.x.

Kinetic modelling of central carbon metabolism in Escherichia coli.

Author information

1
Institute for Systems Biology SPb, Moscow, Russia. kirill.peskov@novartis.com

Abstract

In the present study, we developed a detailed kinetic model of Escherichia coli central carbon metabolism. The main model assumptions were based on the results of metabolic and regulatory reconstruction of the system and thorough model verification with experimental data. The development and verification of the model included several stages, which allowed us to take into account both in vitro and in vivo experimental data and avoid the ambiguity that frequently occurs in detailed models of biochemical pathways. The choice of the level of detail for the mathematical description of enzymatic reaction rates and the evaluation of parameter values were based on available published data. Validation of the complete model of the metabolic pathway describing specific physiological states was based on fluxomics and metabolomics data. In particular, we developed a model that describes aerobic growth of E. coli in continuous culture with a limiting concentration of glucose. Such modification of the model was used to integrate experimental metabolomics data obtained in steady-state conditions for wild-type E. coli and genetically modified strains, e.g. knockout of the pyruvate kinase gene (pykA). Following analysis of the model behaviour, and comparison of the coincidence between predicted and experimental data, it was possible to investigate the functional and regulatory properties of E. coli central carbon metabolism. For example, a novel metabolic regulatory mechanism for 6-phosphogluconate dehydrogenase inhibition by phosphoenolpyruvate was hypothesized, and the flux ratios between the reactions catalysed by enzyme isoforms were predicted.

DATABASE:

The mathematical model described here has been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/peskov/index.html

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