Imperatives for anaerobic high cell density culturing by denitrification: technical and physiological perspectives

Anaerobic HCDC by denitrification is feasible and yields high-quality biomass, but barriers remain to achieving competitive production rates. The CO₂-pH lag appears to be the primary constraint, amplified by incomplete mixing and nitrite toxicity. These factors interact, e.g. mitigating the CO₂-pH lag by lowering the process pH exacerbates nitrite toxicity. Future work should integrate reactor engineering to improve mixing and gas removal and strain selection for tolerance to low pH and nitrite, supported by omics and metabolic modelling to understand denitrifier physiology at high cell density.