Enhanced adenosine production by Bacillus subtilis at condition with comprehensively controlled dissolved oxygen and pH during fermentation

Abstract

Adenosine has potent effects on cardiovascular diseases and has been widely used as an antiarrhythmic agent. To improve its production, we investigated the effects of dissolved oxygen (DO) and pH on production by Bacillus subtilis. Based on the kinetic parameters at different DO levels, we proposed a two-stage DO strategy to control DO level at 30–40% before 20 h of fermentation and 10–20% after 20 h of fermentation, and confirmed that using this strategy could increase adenosine yield to 19.2 g/L in 52 h, which is increased by 78.6, 66.7, 9.5, 18.6, and 32.2%, compared to the conditions with DO uncontrolled or controlled at 0–10, 10–20, 20–30, and 30–40%, respectively. On this basis, pH was adjusted to further boost adenosine production. The results showed that the two-stage DO plus pHshift method was the optimal way for adenosine production, under which, adenosine yield was further improved by 21.4%, reaching 23.3 g/L at 56 h. To our knowledge, this is the first report on adenosine production verifying that the twostage DO plus pH-shift method is effective for enhancing adenosine yield by B. subtilis.