Optimization of technical conditions of producing ribavirin byBacillus subtilis

In this study, the fed-batch fermentation technique was applied to improve the yield of ribavirin produced by Bacillus subtilis AG208-1. Various fermentation substrates and conditions were investigated to identify the optimal concentration of carbon source, Tween-80 and fermentation temperature in the production of ribavirin. The optimal initial glucose concentration was determined to be 120 g/L based on the results of fermentations conducted in a baffled flask. Then, different concentrations of Tween-80 and feeding time were also investigated in this work, respectively. Our results showed that the production of ribavirin by Bacillus subtilis was enhanced when Tween-80 concentration was 0.5%. Furthermore, variable temperature control strategy was predominant factor for ribavirin overproduction and the optimal strategy was: temperature of fermentation at 36 °C from 0 h to 24 h, with a gradual increase in temperature of 2 °C every 6 h. Under the optimal conditions, a final ribavirin concentration of 4.21 g/L was achieved after 60 h.