Optimization of epothilone B production by Sorangium cellulosum using multiple steps of the response surface methodology

Abstract

The anticancer compound epothilone B is biosynthesized by the myxobacterium Sorangium cellulosum; however, the fermentation characteristics for epothilone production in Sorangium cellulosum have not yet been reported. In this study, medium components for the production of epothilone B in the So0157-2 strain of S. cellulosum were statistically screened and optimized. First, the nutrients in the fermentation medium were optimized in one-factor-at-a-time, Plackett-Burman design, and Box-Behnken design experiments. Afterwards, three nutritional parameters were selected for the optimization of epothilone B production in shaking flask cultures using a central composite response surface methodology design; a polynomial equation model that related the medium components and epothilone B yield was established. The data were further analyzed using response surface plots and canonical mathematical model analyses with the SAS 8.0 software. After optimized, the yield of epothilone B increased to 82.0 ± 3 mg/l, 7.2-fold higher than the initial yield (11.3 ± 0.4 mg/l). © 2011 Academic Journals.