Understanding carbon catabolite repression in Escherichia coli using quantitative models

• Carbon catabolite repression (CCR) has motivated important modeling efforts.
• A simplified representation of diauxic growth is useful for comparing existing models.
• Different models, based on different hypotheses, can quantitatively account for CCR.
• Mechanistic models of CCR could be improved by integrating global cell physiology.

Carbon catabolite repression (CCR) controls the order in which different carbon sources are metabolized. Although this system is one of the paradigms of the regulation of gene expression in bacteria, the underlying mechanisms remain controversial. CCR involves the coordination of different subsystems of the cell that are responsible for the uptake of carbon sources, their breakdown for the production of energy and precursors, and the conversion of the latter to biomass. The complexity of this integrated system, with regulatory mechanisms cutting across metabolism, gene expression, and signaling, and that are subject to global physical and physiological constraints, has motivated important modeling efforts over the past four decades, especially in the enterobacterium Escherichia coli. Different hypotheses concerning the dynamic functioning of the system have been explored by a variety of modeling approaches. We review these studies and summarize their contributions to the quantitative understanding of CCR, focusing on diauxic growth in E. coli. Moreover, we propose a highly simplified representation of diauxic growth that makes it possible to bring out the salient features of the models proposed in the literature and confront and compare the explanations they provide.