Fundamental Bioengineering

8Application of Dynamic Models for Optimal Redesign of Cell Factories

Matthias Reuss

Summary

This chapter is about the systems-oriented analysis of the dynamics of cellular systems. This is an important step toward model-predicted rational design for reshaping cellular systems. Whereas the potential and promise of biological systems modeling is substantial, several obstacles are still encountered when addressing the issue of predictive design based on dynamic models. This chapter describes the development of experimental methods that are essential for the identification of kinetic models. On the basis of experiments, following the strategy of the stimulus–response methodology, two different approaches for identification of the dynamic models are described. At the core of the modular concept is the decomposition of the network into manageable subunits. The emphasis of such an approach is the identification of kinetic expression comparable to elucidation of mechanisms in classical enzyme kinetics. In the second approach, canonical approximate models are used emphasizing the systemic context of the individual reactions. With the aid of three examples, strategies for optimal reshaping of networks based on different models are presented. The objective function of these optimizations is first of all the maximization of specific production rates. The optimizations are subject to important constraints, such as crowding, homeostasis, and stable solutions for the dynamic network of the ...