Cyanobacteria are photoautotrophic prokaryotic Gram-negative organisms that exhibit ubiquity across diverse environments. In addition to their ability of fixing atmospheric CO2, these microorganisms produce various secondary metabolites with pharmaceutical and industrial benefits. In nature, one of the most common growth constraints is limitation of nitrogen supply both in marine and terrestrial ecosystems. Nitrogen regulation in cyanobacteria is mediated by the transcriptional regulator NtcA, in conjunction with its co-activator PipX and by the ubiquitous PII signaling protein.

In this study, two unicellular cyanobacterial strains, Synechocystis sp. PCC 6803 (hereafter Synechocystis) and the newly isolated, fast growing strain Synechococcus sp. PCC 11901 (hereafter Synechococcus) are compared based on their response to nitrogen starvation conditions; the process known as "chlorosis". Under optimal growth conditions, Synechocystis displays a doubling time of 12h whereas the fast-growing Synechococcus of only 2-3h of doubling time. During chlorosis, in both species the cellular metabolism experiences a reduction in flux, marked by diminished protein synthesis and anabolic processes. Moreover, the photosynthetic apparatus is compromised, evident in the absence of chlorophyll α and phycobiliproteins, resulting in a transition from a blue-green to yellow color in Synechocystis and white in Synechococcus. Remarkably, Synechococcus also displays a shift in the morphology from rod-shaped to spherical. Chlorotic cells accumulate glycogen in a form of carbon and energy source, subsequently utilized during cellular resuscitation. Transcriptomic analysis of chlorotic cells in Synechocystis reveals heightened expression of the nblA gene, responsible for phycobilisome degradation, and of genes associated with glycogen metabolism.