Two-stage pH control combined with oxygen-enriched air strategies for the highly efficient production of EPA by Mortierella alpina CCFM698 with fed-batch fermentation.

Dissolved oxygen and pH are critical factors influencing cell growth and metabolism. In our previous work, we constructed the recombinant strain Mortierella alpina CCFM698, which has the ability to produce EPA at room temperature. However, our experiments showed that the dissolved oxygen produced by the aeration and agitation of the fermenter was insufficient for cell growth and EPA synthesis by this recombinant strain. Moreover, the optimum pH for cell growth was incompatible with that of EPA accumulation. This study introduced a combined strategy of two-stage pH control with oxygen-enriched air in fed-batch fermentation to facilitate both cell growth and EPA production in M. alpina CCFM698. After 10 days of fermentation in a 7.5 L tank, the biomass production reached 41.2 g/L, with a lipid content of 31.5%, and EPA accounting for 26.7% of total lipids. The final EPA production reached 3.47 g/L, which is the highest yet achieved by M. alpina. This study reveals the critical role of dissolved oxygen and pH control for EPA production of M. alpina, and provides an easy and efficient strategy for industrial production of EPA.