[Control of the metabolic pathway of threonine in E coli. Application of biotechnology].

This paper deals with the application of the metabolic control theory, especially the measurement of control coefficients, to the threonine pathway in E. coli. The control coefficient of a step on a metabolic flux quantitatively assesses the flux response to the step variations. This concept is particularly relevant both in pathological situations (decrease in the activity of an enzymatic step in the metabolism) and in biotechnologies, where, on the contrary steps are amplified. Measurement of the control coefficients of the steps of a metabolic network makes it possible to know those whose amplification should lead to a simultaneous increase in the fluxes. We have applied these concepts to threonine biosynthesis from aspartate in E. coli. The threonine pathway starting from aspartate involves five steps catalyzed by five enzyme activities: aspartokinase (AK), aspartate-semialdehyde-dehydrogenase (ASA-DH), homoserine dehydrogenase (HDH), homoserine kinase (HK) and hreonine synthetase activity (TS). Measurement of the control coefficient of the first step (AK, insensitive to threonine inhibition in the studied strain) has shown that it controls threonine production weakly. Our study has revealed a hitherto unknown inhibition of homoserine kinase activity by lysine. Mathematical modeling of this metabolic pathway has been undertaken to better understand our experimental results.