CURRENT PERSPECTIVE ESSAY A Renaissance of Metabolite Sensing and Signaling: From Modular Domains to Riboswitches

The ability of an organism to sense cellular, extracellular, or environmentally derived signals, to integrate that information, and to respond appropriately is broadly termed signal transduction and is fundamental to the survival of that organism. In our first biochemistry course, most of us were exposed to specific metabolites, but likely only in terms of being intermediates or cofactors of a metabolic pathway and as allosteric activators or inhibitors of key regulatory enzymes. This view of metabolites is rapidly changing as recent work across a broad spectrum of organisms has shown certain metabolites to be signaling molecules that coregulate and integrate metabolic status with other fundamental cellular events, such as transcription, translation, covalent modification of signal transduction proteins, and membrane channel function. This essay will highlight some of these discoveries using the bestcharacterized examples from a selection of organisms, ultimately comparing these to higher plants and examining what might be gleaned from comparative genomics of metabolite-mediated signal transduction.