Inorganic carbon is the major macronutrient required by organisms utilizing oxygenic photosynthesis for autotrophic growth. Aquatic photoautotrophic organisms are dependent upon a CO 2 concentrating mechanism (CCM) to overcome the poor CO 2 -affinity of the major carbon-fixing enzyme, ribulose-bisphosphate carboxylase/oxygenase (Rubisco). The CCM involves the active transport of inorganic forms of carbon (C i ) into the cell to increase the CO 2 concentration around the active site of Rubisco. It employs both bicarbonate transporters and redox-powered CO 2 -hydration enzymes coupled to membranous NDH-type electron transport complexes that collectively produce C i concentrations up to a 1000-fold greater in the cytoplasm compared to the external environment. The CCM is regulated: a high affinity CCM comprised of multiple components is induced under limiting external Ci concentrations. The LysR-type transcriptional regulator CcmR has been shown to repress its own expression along with structural genes encoding high affinity C i transporters distributed throughout the genome of Synechocystis sp. PCC 6803. While much has been learned about the structural genes of the CCM and the identity of the transcriptional regulators controlling their expression, little is known about the physiological signals that elicit the induction of the high affinity CCM. Here CcmR is studied to identify metabolites that modulate its transcriptional repressor activity. Using surface plasmon resonance (SPR) α­ketoglutarate (α-KG) and the oxidized form of nicotinamide adenine dinucleotide phosphate (NADP + ) have been identified as the co-repressors of CcmR. Additionally, ribulose­1,5­bisphosphate (RuBP) and 2­phosphoglycolate (2­PG) have been confirmed as co-activators of CmpR which controls the expression of the ABC-type bicarbonate transporter.