Description:
<p>Cyanobacteria have efficient carbon concentration mechanisms and suppress photorespiration in response to inorganic carbon (Ci) limitation. We studied intracellular Ci limitation in the slow-growing CO₂/HCO₃⁻ -uptake mutant Δ<italic>ndhD3</italic>(for<italic>NADH dehydrogenase subunit D3)/ndhD4</italic>(for<italic>NADH dehydrogenase subunit D4</italic>)/<italic>cmpA</italic>(for<italic>bicarbonate transport system substrate-binding protein A)/sbtA</italic>(for<italic>sodium-dependent bicarbonate transporter A</italic>): Δ4 mutant of<italic>Synechocystis</italic>sp. PCC 6803. When cultivated under high-CO₂ conditions, Δ4 phenocopies wild-type metabolic and transcriptomic acclimation responses after the shift from high to low CO₂ supply. The Δ4 phenocopy reveals multiple compensation mechanisms and differs from the preacclimation of the transcriptional Ci regulator mutant Δ<italic>ndhR</italic>(for<italic>ndhF3 operon transcriptional regulator</italic>). Contrary to the carboxysomeless Δ<italic>ccmM</italic>(for<italic>carbon dioxide concentrating mechanism protein M</italic>) mutant, the metabolic photorespiratory burst triggered by shifting to low CO₂ is not enhanced in Δ4. However, levels of the photorespiratory intermediates 2-phosphoglycolate and glycine are increased under high CO₂. The number of carboxysomes is increased in Δ4 under high-CO₂ conditions and appears to be the major contributing factor for the avoidance of photorespiration under intracellular Ci limitation. The Δ4 phenocopy is associated with the deregulation of Ci control, an overreduced cellular state, and limited photooxidative stress. Our data suggest multiple layers of Ci regulation, including inversely regulated modules of antisense RNAs and cognate target messenger RNAs and specific trans-acting small RNAs, such as the posttranscriptional PHOTOSYNTHESIS REGULATORY RNA1 (PsrR1), which shows increased expression in Δ4 and is involved in repressing many photosynthesis genes at the posttranscriptional level. In conclusion, our insights extend the knowledge on the range of compensatory responses of<italic>Synechocystis</italic>sp. PCC 6803 to intracellular Ci limitation and may become a valuable reference for improving biofuel production in cyanobacteria, in which Ci is channeled off from central metabolism and may thus become a limiting factor.</p>