Comparative analysis of some models of gene regulation in mixed-substrate microbial growth.

Mixed-substrate microbial growth is of fundamental interest in microbiology and bioengineering. Several mathematical models have been developed to account for the genetic regulation of such systems, especially those resulting in diauxic growth. In this work, we compare the dynamics of three such models (Narang, 1998a. The dynamical analogy between microbial growth on mixtures of substrates and population growth of competing species. Biotechnol. Bioeng. 59, 116-121; Thattai and Shraiman, 2003. Metabolic switching in the sugar phosphotransferase system of Escherichia coli. Biophys. J. 85(2), 744-754; Brandt et al., 2004. Modelling microbial adaptation to changing availability of substrates. Water Res. 38, 1004-1013). We show that these models are dynamically similar--the initial motion of the inducible enzymes in all the models is described by the Lotka-Volterra equations for competing species. In particular, the prediction of diauxic growth corresponds to "extinction" of one of the enzymes during the first few hours of growth. The dynamic similarity occurs because in all the models, the inducible enzymes possess properties characteristic of competing species: they are required for their own synthesis, and they inhibit each other. Despite this dynamic similarity, the models vary with respect to the range of dynamics captured. The Brandt et al. model always predicts the diauxic growth pattern, whereas the remaining two models exhibit both diauxic and non-diauxic growth patterns. The models also differ with respect to the mechanisms that generate the mutual inhibition between the enzymes. In the Narang model, mutual inhibition occurs because the enzymes for each substrate enhance the dilution of the enzymes for the other substrate. The Brandt et al. model superimposes upon this dilution effect an additional mechanism of mutual inhibition. In the Thattai and Shraiman model, the mutual inhibition is entirely due to competition for the phosphoryl groups. For quantitative agreement with the data, all models must be modified to account for specific mechanisms of mutual inhibition, such as inducer exclusion.