Functional and structural insights into cyanobacterial CO₂ concentrating mechanisms: from compartmentalization to regulation

Cyanobacteria are photoautotrophic microorganisms that fix CO₂ through oxygenic photosynthesis during the day and rely on heterotrophic metabolism at night. In nature, the availability of inorganic carbon (Ci) is often limited, posing a major constraint on photosynthetic efficiency. To overcome this, cyanobacteria have evolved a sophisticated CO₂-concentrating mechanism (CCM) that enhances the catalytic performance of the primary carboxylating enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO). The CCM functions by elevating intracellular CO₂ concentrations around RubisCO to suppress its oxygenase activity and enhance CO₂ fixation efficiency. Central to this system is the carboxysome, a proteinaceous microcompartment that encapsulates RubisCO and carbonic anhydrase, facilitating efficient conversion of bicarbonate (HCO₃ ^–) to CO₂ and its subsequent fixation. This is complemented by multiple Ci transporters that mediate active uptake of CO₂ and HCO₃ ^–. Five major transport systems have been characterized: two specialized NDH-1 complexes for CO₂ transport and its conversion into HCO₃ ^–, and SbtA, BicA, and BCT1 for HCO₃ ^– uptake. Recent structural studies on CCM uptake systems have revealed key mechanisms of HCO₃ ^– transport, CO₂ hydration and transport coupling. These insights provided a deeper understanding of how these systems enhance Ci acquisition and maintain photosynthetic efficiency across diverse environmental conditions and various CO₂ regimes. Moreover, the CCM is tightly regulated at both transcriptional and post-translational levels to balance energy usage and carbon demand. This review outlines our current insights into the molecular architecture, transport dynamics, and regulatory networks of the cyanobacterial CCM, emphasizing its critical role in photosynthesis and its potential as a model for bioengineering enhanced CO₂ fixation or for engineering synthetic bacterial microcompartments.