Integrated strategy of pH-shift and glucose feeding for enhanced production of bioactive Antrodin C in submerged fermentation of Antrodia camphorata

Antrodin C is one of the most potent bioactive components produced by the medicinal mushroom Antrodia camphorata. However, almost all studies in this field have focused on the biological activity of Antrodin C and relatively rare information has been reported regarding the biosynthetic process of Antrodin C. In this study, the strategies of pH-shift and glucose feeding for enhanced production of Antrodin C in submerged fermentation of A. camphorata were successfully applied in stirred bioreactors. The critical parameters for pH-shift and glucose feeding were systematically investigated. On one hand, the optimal culture pH for cell growth was distinct with Antrodin C biosynthesis and the maximum Antrodin C production was obtained by maintaining the first-stage culture at initial pH 4.5 and adjusted to 6.0 at day 8. On the other hand, it was beneficial for the Antrodin C accumulation with the initial glucose concentration of 40 g/L and feeding glucose to keep the residual sugar above 10 g/L. The maximum Antrodin C production (1,549.06 mg/L) was about 2.1-fold higher than that of control in 15-L stirred bioreactors by taking advantage of the integrated strategy of pH-shift and glucose feeding. These results would be helpful for the design of a highly efficient Antrodin C biosynthesis process.