Optimization of biotechnological systems through geometric programming

A new method is proposed for this task. We show here that the model format of a Generalized Mass Action (GMA) system may be optimized very efficiently with techniques of geometric programming. We briefly review the basics of GMA systems and of geometric programming, demonstrate how the latter may be applied to the former, and illustrate the combined method with a didactic problem and two examples based on models of real systems. The first is a relatively small yet representative model of the anaerobic fermentation pathway in S. cerevisiae, while the second describes the dynamics of the tryptophan operon in E. coli. Both models have previously been used for benchmarking purposes, thus facilitating comparisons with the proposed new method. In these comparisons, the geometric programming method was found to be equal or better than the earlier methods in terms of successful identification of optima and efficiency.GMA systems are of importance, because they contain stoichiometric, mass action and S-systems as special cases, along with many other models. Furthermore, it was previously shown that algebraic equivalence transformations of variables are sufficient to convert virtually any types of dynamical models into the GMA form. Thus, efficient methods for optimizing GMA systems have multifold appeal.Model based optimization of biotechnological processes is a key step towards the establishment of rational strategies for yield improvement, be it through genetic engineering, refined setting of operating conditions or both. As such, it is a key element in the rapidly emerging field of metabolic engineering [1,2]. Optimization tasks involving living organisms are notoriously difficult, because they almost always involve large numbers of variables, representing biological components that dominate cell operation, and must account for multitudinous and complex nonlinear interactions among them [3]. The steady increase in the ready availability of computing power has somewhat all