DYNAMIC SENSITIVITY ANALYSIS FOR METABOLIC SYSTEMS

This paper illustrates a new method for the determination of steady-st ate and time-dependent control coefficients to be obtained from dynami c metabolic models. This method is based on the rapidly advancing tech niques for monitoring and modelling intracellular pool changes followi ng extracellular system perturbation. In addition to the attraction of computing steady-state and dynamic flux control coefficients and conc entration control coefficients, the importance of investigating both c ontrol exercised by enzyme amount and kinetic enzyme properties is hig hlighted. The application of this new method is illustrated with the a id of a simple metabolic model. Further, it is shown that control of i ntracellular dynamics can also be suitably affected through careful se lection of dynamic extracellular system stimulation. The proposed meth od reveals the hierarchic structure of effective system manipulation a nd thus constitutes a valuable source of information for the optimizat ion of metabolic engineering applications. (C) 1997 Elsevier Science L td.