A computer simulation of the threonine-synthesis pathway in Escherichia coli Tir-8 has been developed based on our previous measurements of the kinetics of the pathway enzymes under near-physiological conditions. The model successfully simulates the main features of the time courses of threonine synthesis previously observed in a cell-free extract without alteration of the experimentally determined parameters, although improved quantitative fits can be obtained with small parameter adjustments. At the concentrations of enzymes, precursors and products present in cells, the model predicts a threonine-synthesis flux close to that required to support cell growth. Furthermore, the first two enzymes operate close to equilibrium, providing an example of a near-equilibrium feedback-inhibited enzyme. The predicted flux control coefficients of the pathway enzymes under physiological conditions show that the control of flux is shared between the first three enzymes: aspartate kinase, aspartate semialdehyde dehydrogenase and homoserine dehydrogenase, with no single activity dominating the control. The response of the model to the external metabolites shows that the sharing of control between the three enzymes holds across a wide range of conditions, but that the pathway flux is sensitive to the aspartate concentration. When the model was embedded in a larger model to simulate the variable demands for threonine at different growth rates, it showed the accumulation of free threonine that is typical of the Tir-8 strain at low growth rates. At low growth rates, the control of threonine flux remains largely with the pathway enzymes. As an example of the predictive power of the model, we studied the consequences of over-expressing different enzymes in the pathway.
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June 2001
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Research Article|
May 24 2001
Control of the threonine-synthesis pathway in Escherichia coli: a theoretical and experimental approach
Christophe CHASSAGNOLE;
Christophe CHASSAGNOLE
∗INSERM EMI 9929, University Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France
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David A. FELL;
David A. FELL
∗INSERM EMI 9929, University Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France
†School of Biological and Molecular Sciences, Oxford Brookes University, Oxford OX3 0BP, U.K.
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Badr RAÏS;
Badr RAÏS
∗INSERM EMI 9929, University Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France
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Bernard KUDLA;
Bernard KUDLA
‡52 rue de Gometz, 91470 Les Molières, France
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Jean-Pierre MAZAT
Jean-Pierre MAZAT
1
∗INSERM EMI 9929, University Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France
1To whom correspondence should be addressed (e-mail JP.Mazat@phys-mito.u-bordeaux2.fr).
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Publisher: Portland Press Ltd
Received:
October 06 2000
Revision Received:
January 02 2001
Accepted:
March 05 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 356 (2): 433–444.
Article history
Received:
October 06 2000
Revision Received:
January 02 2001
Accepted:
March 05 2001
Citation
Christophe CHASSAGNOLE, David A. FELL, Badr RAÏS, Bernard KUDLA, Jean-Pierre MAZAT; Control of the threonine-synthesis pathway in Escherichia coli: a theoretical and experimental approach. Biochem J 1 June 2001; 356 (2): 433–444. doi: https://doi.org/10.1042/bj3560433
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