CO₂ - intrinsic product, essential substrate, and regulatory trigger of microbial and mammalian production processes

Carbon dioxide formation mirrors the final carbon oxidation steps of aerobic metabolism in microbial and mammalian cells. As a consequence, CO₂/HCO₃- dissociation equilibria arise in fermenters by the growing culture. Anaplerotic reactions make use of the abundant CO₂/HCO₃- levels for refueling citric acid cycle demands and for enabling oxaloacetate-derived products. At the same time, CO₂ is released manifold in metabolic reactions via decarboxylation activity. The levels of extracellular CO₂/HCO₃- depend on cellular activities and physical constraints such as hydrostatic pressures, aeration, and the efficiency of mixing in large-scale bioreactors. Besides, local CO₂/HCO₃- levels might also act as metabolic inhibitors or transcriptional effectors triggering regulatory events inside the cells. This review gives an overview about fundamental physicochemical properties of CO₂/HCO₃- in microbial and mammalian cultures effecting cellular physiology, production processes, metabolic activity, and transcriptional regulation.