The phosphotransferase system in Escherichia coli is a transport and sensory system and, in this function, is one of the key players of catabolite repression. Mathematical modelling of signal transduction and gene expression of the enzymes involved in the transport of carbohydrates is a promising approach in biotechnology, as it offers the possibility to achieve higher production rates of desired components. In this article, the relevance of methods and approaches concerning mathematical modelling in systems biology is discussed by assessing and comparing two comprehensive mathematical models that describe catabolite repression. The focus is thereby on modular modelling with the relevant input in the central modules, the impact of quantitative model validation, the identification of control structures and the comparison of model predictions with respect to the available experimental data.