Enhancing Docosahexaenoic Acid Production by Schizochytrium sp. via Periodic Hydrogen Peroxide and p-Aminobenzoate Control

In producing docosahexaenoic acid (DHA) with Schizochytrium sp., the production yield of DHA can be effectively increased through using hydrogen peroxide (H2O2) and controlling its concentration at the desired level, since H2O2 is a common regulatory mediator for lipid accumulation in oleaginous microorganisms. However, when exposed to the environment of oxidative stress induced by the long-term exogenous addition of H2O2 over an extended time span, cells’ metabolic activity would be gradually decreased or even stopped, which ultimately results in a limited duration for producing DHA efficiently. In fact, the severe accumulation of ROS cannot be avoided when implementing the normal DHA fermentation batch without the use of exogenous H2O2 because of the necessity of supplying a mass of oxygen for cell respiration. Aiming to overcome these issues, a novel periodic feeding strategy for H2O2 and p-aminobenzoate was proposed, and the underlying principle of this strategy is that the substantial harm inflicted on cells due to their continuous exposure to the oxidative stress environment can be effectively alleviated through the implementation of a recovery treatment (p-aminobenzoate, reducing agent) subsequent to the environmental stimulus. When using this strategy, it was achieved that, concurrently, activities of the vital enzymes participating in lipid biosynthesis were maintained at their maximum levels and the maintenance coefficient of glucose reduced to its minimum level (0.0034 1/h vs. 0.0027 1/h) by controlling ROS concentration at lower and desired levels, and thus DHA concentration reached the maximum value of 1.49 ± 0.20 g/L, with a 49% increase compared to the control group.