Scale-up of rifamycin B fermentation with Amycolatoposis mediterranei.

Study of the effect of dissolved oxygen and shear stress on rifamycin B fermentation with A. mediterranei XC 9-25 showed that rifamycin B fermentation with Amycolatoposis mediterranei XC 9-25 needs high dissolved oxygen and is not very sensitive to shearing stress. The scale-up of rifamycin B fermentation with A. mediterranei XC 9-25 from a shaking flask to a 15 L fermentor was realized by controlling the dissolved oxygen to above 25% of saturation in the fermentation process, and the potency of rifamycin B fermentation in the 15 L fermentor reached 10 g/L after 6-day batch fermentation. By continuously feeding glucose and ammonia in the fermentation process, the potency of rifamycin B fermentaion in the 15 L fermentor reached 18.67 g/L, which was 86.65% higher than that of batch fermentation. Based on the scale-up principle of constantly aerated agitation power per unit volume, the scale-up of rifamycin B fed-batch fermentation with continuous feed from a 15 L fermentor to a 7 m(3) fermentor and further to a 60 m(3) fermentor was realized successfully. The potency of rifamycin B fermentation in the 7 m(3) fermentor and in the 60 m(3) fermentor reached 17.25 g/L and 19.11 g/L, respectively.