Coordinating carbon and nitrogen metabolic signaling through the cyanobacterial global repressor NdhR

Significance The homeostasis of carbon and nitrogen metabolism needs to be tightly regulated for cell acclimation to fluctuating environments. The related metabolic pathways are ultimately coordinated by the master transcription factors that sense the intracellular metabolites. We report here biochemical, structural, and functional studies of the fine regulation of the transcriptional repressor NAD(P)H dehydrogenase regulator (NdhR). Two key metabolites, 2-OG from the Krebs cycle and 2-PG from photorespiration, have opposite effects on the regulatory activity of NdhR. We propose that 2-OG and 2-PG function together as indicators of intracellular carbon/nitrogen status and that NdhR senses these two effectors in a mutually exclusive manner. Our findings together with previous studies provide a model for the fine coordination of carbon and nitrogen metabolic signaling.