Abstract
The anticancer compound epothilone B is biosynthesized by the myxobacteriumSorangium 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). Key words: Myxobacterium, Sorangium cellulosum, epothilone B, statistical optimization, response surface methodology.
Highlights
Epothilones, which are naturally produced by the myxobacterium Sorangium cellulosum (Gerth et al, 1996; Höfle et al, 1996), are anticancer agents that mimic the anticancer mechanisms of paclitaxel (Bollag et al, 1995; Kowalski et al, 1997)
The anticancer compound epothilone B is biosynthesized by the myxobacterium Sorangium cellulosum; the fermentation characteristics for epothilone production in Sorangium cellulosum have not yet been reported
We investigated the relationships between the production of epothilone B in S. cellulosum strain So0157-2 and the composition of the culture medium and further optimized the concentration for this compound
Summary
Epothilones, which are naturally produced by the myxobacterium Sorangium cellulosum (Gerth et al, 1996; Höfle et al, 1996), are anticancer agents that mimic the anticancer mechanisms of paclitaxel (that is, microtubule stabilization) (Bollag et al, 1995; Kowalski et al, 1997). Several reports have attempted to improve the production of epothilones. We made mutations in epothilone-producing Sorangium strains to improve production (Gong et al, 2007). The effects of culture medium components on the production of epothilones in natural Sorangium producers have not been reported, most likely due to the difficulties in manipulating S. cellulosum strains (Reichenbach and Dworkin, 1992). We investigated the relationships between the production of epothilone B in S. cellulosum strain So0157-2 and the composition of the culture medium and further optimized the concentration for this compound
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