Coordination of bacterial proteome with metabolism by cAMP signalling

摘要

Cyclic AMP (cAMP) dependent catabolite repression effect in E. coli is among the most intensely studied regulatory processes in biology. However, the physiological function(s) of cAMP signalling and its molecular triggers remain elusive. Here we use a quantitative physiological approach to show that cAMP signalling tightly coordinates the cell’s protein expression program with its metabolic needs during exponential cell growth: The expression of carbon catabolic genes increased linearly with decreasing growth rates upon limitation of carbon influx, but decreased linearly with decreasing growth rate upon limitation of nitrogen or sulfur influx. In contrast, the expression of biosynthetic genes exhibited the opposite linear growth-rate dependence as the catabolic genes. A coarse-grained mathematical model provides a quantitative framework for understanding and predicting gene expression responses to catabolic and anabolic limitations. A scheme of integral feedback control featuring the inhibition of cAMP signalling by metabolic precursors is proposed and validated. These results reveal a key physiological role of cAMP-dependent catabolite repression: to ensure that proteomic resources are spent on distinct metabolic sectors as needed in different nutrient environments. Our finding underscores the power of quantitative physiology in unravelling the underlying functions of complex molecular signalling networks.