Diurnal rhythm causes metabolic crises in the cyanobacterial mutants of c-di-AMP signaling cascade.

The photoautotrophic lifestyle of cyanobacteria has to cope with the successive diurnal changes. We previously highlighted a unique function of the carbon control protein, SbtB, and its effector molecule c-di-AMP, for nighttime survival through the regulation of glycogen anabolism. However, the extent to which c-di-AMP and SbtB impact the cellular metabolism for day-night survivability remained elusive. To gain a better understanding, we compared the metabolomic and proteomic landscapes of Δ and the c-di-AMP-free (Δ) mutants of sp. PCC 6803. While our results indicated that the cellular role of SbtB is restricted to carbon/glycogen metabolism, the diurnal lethality of Δ seemed to be a sum of the dysregulation of multiple processes, including photosynthesis and redox regulation. Further, we showed an impact of c-di-AMP on central carbon/nitrogen metabolism, which is linked to NtcA transcription regulation and highlighted by an imbalance of glutamine/glutamate ratio as well as the reduction of arginine pathway metabolites. We further identified the HCO uptake systems, BicA and BCT1, as novel SbtB targets, in agreement with its broader role in regulating carbon homeostasis.