Regulation and control of metabolic fluxes in microbes

After about ten years of research renaissance in metabolism, the present challenge is to understand how metabolic fluxes are controlled by a complex interplay of overlapping regulatory mechanisms. Reconstruction of various regulatory network topologies is steaming, illustrating that we underestimated the broad importance of post-translational modifications such as enzyme phosphorylation or acetylation for microbial metabolism. With the growing topological knowledge, the functional relevance of these regulatory events becomes an even more pressing need. A major knowledge gap resides in the regulatory network of protein–metabolite interactions, simply because we lacked pertinent methods for systematic analyses – but a start has now been made. Perhaps most dramatic was the conceptual shift in our perception of metabolism from an engine of cellular operation to a generator of input and feedback signals for regulatory circuits that govern many important decisions on cell proliferation, differentiation, death, and naturally metabolism.

► Overlapping regulatory mechanisms control metabolic fluxes. ► Post-translational modifications are abundant regulators of microbial metabolism. ► Input–output regulatory functions are most advanced for transcriptional networks. ► Metabolic feedback into regulatory networks governs many cellular decisions. ► Kinetic models are crucial to turn data into understanding of metabolic control.