A combined feeding strategy for enhancing mycophenolic acid production by fed-batch fermentation in Penicillium brevicompactum

A combined feeding strategy for enhancing mycophenolic acid production by fed-batch fermentation in Penicillium brevicompactum was investigated. In a 7 L fermenter, the relevant parameters of CN-feeding strategy (F-CN), pH shift strategy (F-pH), and Met-feeding strategy (F-Met) were inspected and analyzed during the synthesis phase of MPA fermentation after 120 h. Compared to the fed-batch fermentation, the three strategies improved the MPA production to 2.23, 1.92, and 2.03 g/L, increased by 29.65, 11.63, and 18.02%, respectively. Based on the above results, a combined strategy (F-CPM) was designed. Under F-CPM strategy, the maximum dry cell weight (DCWmax) reached 45.77 g/L at 240 h, and the maximum MPA production (Pmax) reached a higher level of 2.68 g/L, increased by 55.81%. The combined feeding strategy can effectively reduce the impact of substrate inhibition and improve MPA productivity. Thus, our work offered a new idea for industrialization of MPA fermentation with conventional industrial equipment.