Optimization of Fermentation Medium for Epothilones Production with Sequential Statistical Approach

A sequential statistical approach was applied to optimizing the fermentation medium of epothilones(Epos) production by means of a mutant which was obtained by treating polyangium cellulosum ATCC 15384 with nitrite and ultraviolet. The effects of different carbon sources and nitrogen sources on the fermentation medium were tested, and the suitable ones were selected. Then a uniform design was employed to design the experiments. A linear model was developed for identifying the significant components in fermentation medium; while a third degree polynomial model was used for studying the relationship between the concentration of the components in fermentation medium and the yield of Epos(YEPs). A pattern search method was used for searching the optimum fermentation medium in the test space, which was as follows(g/L): potassium nitrate 8.00, soybean peptone 17.60, potassium hydrogen phosphate 1.00, beef extraction 6.46, yeast extraction 1.00, calcium chloride 0.25, sodium chloride 1.00 and ferric chloride 0.02. The optimum fermentation medium was expected to result in a yield of Epos(YEPs) of 2.48 mg/L. The validation experiments with the optimum medium were performed in triplicate and the average yield of Epos was 2.45 mg/L which was 7.78 times higher than that of Epos prepared without optimization.