The conserved small protein SniP3 is a regulator of primary metabolism in cyanobacteria

Cyanobacteria are oxygenic phototrophs that are promising for the CO 2 -neutral production of a variety of compounds using sunlight. In the environment, they are regularly exposed to fluctuating environmental conditions, and understanding their acclimation responses is advantageous for exploiting their full potential. Particularly, the availability of CO 2 and combined nitrogen sources varies in many aquatic habitats. Therefore, the cyanobacterial growth needs to be adjusted towards changing external C/N conditions. In recent years, many small proteins have been newly discovered that are involved in the metabolic acclimation of cyanobacteria. In the present study, we investigated the role of SniP3, a well-conserved, 3 kDa nitrogen-starvation-induced protein, that is primarily localized on thylakoid membranes. Deletion of sniP3 resulted in a non-bleaching phenotype, reduced glycogen accumulation under N-deplete conditions and many more distinct metabolic alterations. In contrast, the increased amounts of the signaling metabolite 2-oxoglutarate and the overall transcriptomic changes upon N depletion remained comparable in mutant and wild-type cells. The SniP3 interactome revealed glyceraldehyde-3-phosphate dehydrogenase 2 (Gap2) as main specific interaction partner. Gap2 activity was lowered in cells of the sniP3 mutant, while the activity of recombinant Gap2 was stimulated in the presence of the soluble N-terminal part of SniP3. Consistent with the interaction between SniP3 and Gap2, the sniP3 mutant was unable to grow heterotrophically with glucose in the dark. Collectively, our results imply that SniP3 plays an important role in the regulation of the cyanobacterial metabolism under fluctuating C/N conditions.