Medium optimization for enhanced production of Rifamycin B by Amycolatopsis mediterranei S699: Combining a full factorial design and a statistical approach

摘要

This paper describes improved optimization method that combines the Plackett-Burman design, a full factorial design and the response surface method, which were used to optimize the medium for the production of rifamycin B by Amycolatopsis mediterranei S699. The five nutrients used to amend the medium were preliminary selected from 15 medium components based on the results of the Plackett-Burman design experiments and subsequent screening process using the full factorial design experiments was performed. Glucose, (NH_4)_2SO_4, and corn steep liquor were found to be the best nutrients for the optimization of rifamycin B productions, and central composite design experiments indicated that the optimal concentrations of these nutrients were 63 g/L, 7.9 g/L, and 10 g/L, respectively. A bioreactor culture was used to investigate the production characteristics obtained when Amycolatopsis mediterranei S699 was grown in the determined optimum medium. Although cell growth stopped at 88 h, rifamycin B production continued, reaching its maximum value at the end of the experiment (172 h) after the glucose in the medium was completely consumed. The maximum cell concentration and rifamycin B titer were 8.6 g/L and 1260 mg/L, respectively. The combined optimization method described here is new and effective method for screening carbon and nitrogen sources as well as determining their optimum levels.