The Novel PII-Interacting Regulator PirC (Sll0944) Identifies 3-Phosphoglycerate Mutase (PGAM) as Central Control Point of Carbon Storage Metabolism in Cyanobacteria

Nitrogen limitation imposes a major transition in the life-style of non-diazotrophic cyanobacteria, which is regulated via a complex interplay of regulatory factors, involving, the nitrogen-specific transcription factor NtcA and the pervasive signal processor PII. Immediately upon nitrogen-limitation, newly fixed carbon is re-directed towards glycogen synthesis. How the metabolic switch for distributing fixed carbon to either glycogen or cellular building blocks is operated was poorly understood. Here we identify from Synechocystis sp. PCC 6803 a novel PII interactor, PirC, (Sll0944) that controls 3-phosphoglycerate mutase (PGAM), the enzyme that deviates newly fixed CO 2 towards lower glycolysis. PirC acts as competitive inhibitor of PGAM and this interaction is tuned by PII/2-oxoglutarate. High oxoglutarate release PirC from PII-complex to inhibit PGAM. Accordingly, PirC deficient mutant, as compared to the wild-type, shows strongly reduced glycogen levels upon nitrogen deprivation whereas polyhydroxybutyrate granules are over-accumulated. Metabolome analysis revealed an imbalance in 3-phosphoglycerate to pyruvate levels in the PirC mutant, conforming that PirC controls the carbon flux in cyanobacteria via mutually exclusive interaction with either PII or PGAM.