Enhanced production of Fumigaclavine C in liquid culture of Aspergillus fumigatus under a two-stage process

•A novel two-stage process was proposed to enhance the production of FC.•Changes in kinetic profiles had been investigated under different process.•Predictive modeling of the two-stage process had been developed.•Scale-up experiments had been achieved in a combined stirred–static bioreactor. Fumigaclavine C (FC) produced by Aspergillus fumigatus is a conidiation associated ergot alkaloid with strong anti-inflammatory activity. However, its wide application has been severely limited by low FC production from submerged culture. In this work, a novel two-stage culture process by combining shake culture with static culture was proposed to enhance the production of FC. After the process optimization, the FC production reached 62.7mg/L, which was significantly higher than ever report. For scaling up this new culture process, the gas–liquid interfacial area per unit volume (Agas–liq) was identified as the key factor. The results showed that in a combined stirred–static bioreactor system, a maximum FC production (58.97mg/L) was obtained at an Agas–liq value of 1.30cm2/mL. These results demonstrated that two-stage culture is an efficient strategy to enhance FC production and the information obtained will be useful to production of this powerful bioactive compound on a large scale.