Control and Thermodynamics of Microbial Growth: Rational Tools for Bioengineering

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Abstract
The metabolic control theory (MCT) provides an exact and quantitative framework for the description of microbial growth. It gives a value for the contribution of each specific individual step (or ensemble) in the total control of fluxes in a complex metabolic network (such as a microbial cell) by means of socalled flux control coefficients. Therefore, MCT is an interesting tool for modeling microbial growth and product formation. The present review focuses on the application of the concepts of MCT of a relatively simple model of microbial growth. In this model (which was already used in the mosaic nonequilibrium thermodynamic approach of Westerhoff and Van Dam (1987) Elsevier), the metabolism is lumped together in three essential steps, i.e., catabolism (all energyliberating processes), anabolism (in which ATP is used for biosynthesis) and leak (ATP hydrolysis without coupling to anabolism or catabolism). According to MCT, it is a priori not justified to describe growth by one limiting step (substrate or enzyme). Inspection of the flux control coefficients of the anabolic system, catabolic system, and the leak on the rate of growth revealed interesting characteristics about the control structure in a microbial cell. For instance, the control of the anabolic system on the rate of growth is, in principle, a constant (i.e., not dependent on driving forces). Furthermore, the control of the leak on the rate of growth is not always negative. This procedure can be used to screen microbial metabolism for clusters with control.