Metabolite-level regulation of enzymatic activity controls awakening of cyanobacteria from metabolic dormancy.

Transitioning into and out of dormancy is a crucial survival strategy for many organisms. In unicellular cyanobacteria, surviving nitrogen-starved conditions involves tuning down their metabolism and reactivating it once nitrogen becomes available. Glucose-6-phosphate dehydrogenase (G6PDH), the enzyme that catalyzes the first step of the oxidative pentose phosphate (OPP) pathway, plays a key role in this process. G6PDH is produced at the onset of nitrogen starvation but remains inactive in dormant cells, only to be rapidly reactivated when nitrogen is restored. In this study, we investigated the mechanisms underlying this enzymatic regulation and found that G6PDH inactivation is primarily due to the accumulation of inhibitory metabolites. Moreover, our findings demonstrate that metabolite-level regulation is the driving force behind the resuscitation program. This study highlights the critical importance of metabolite-level regulation in ensuring rapid and precise enzymatic control, enabling microorganisms to swiftly adapt to environmental changes and undergo developmental transitions.