Dynamic sensitivity analysis for metabolic systems

This paper illustrates a new method for the determination of steady-state and time-dependent control coefficients to be obtained from dynamic metabolic models. This method is based on the rapidly advancing techniques for monitoring and modelling intracellular pool changes following extracellular system perturbation. In addition to the attraction of computing steady-state and dynamic flux control coefficients and concentration control coefficients, the importance of investigating both control exercised by enzyme amount and kinetic enzyme properties is highlighted. The application of this new method is illustrated with the aid of a simple metabolic model. Further, it is shown that control of intracellular dynamics can also be suitably affected through careful selection of dynamic extracellular system stimulation. The proposed method reveals the hierarchic structure of effective system manipulation and thus constitutes a valuable source of information for the optimization of metabolic engineering applications. (C) 1997 Elsevier Science Ltd.