Metabolite changes signal genetic regulatory mechanisms for robust cell behavior

Abstract

Exploiting mechanisms of utilizing the sugar D-galactose in Escherichia coli as a model system, we explored the consequences of accumulation of critical intermediates of the D-galactose metabolic pathways by monitoring cell growth, metabolites, and transcript profiles. These studies revealed both metabolic network changes far from the D-galactose pathway and changes in the global gene regulatory network. The concentration change of a critical intermediate disturbs the equilibrium state, generating a ripple effect through several metabolic pathways that ends up signaling up- or downregulation of specific sets of genes in a programmed manner to cope with the imbalance. Such long-range effects on metabolites and genetic regulatory mechanisms not only may be a common feature in bacteria but very likely operate during cellular development and differentiation in higher organisms as well as in disease cells, like cancer cells