Optimization of the Fermentation Medium for Epothilones High-Producing Strain Using Response Surface Methodology Coupled with Desirability Function

In this paper, response surface methodology was applied to optimize the fermentation medium for epothilones high-producing strain. Considering the activity of epothilones, desirability function was employed to establish the criterion for the optimization. Suitable carbon sources and nitrogen sources were chosen by single-factor test firstly. Plackett-Burman design combined with the linear model was applied to identify the significant components in the fermentation medium. Based on the results of the Plackett-Burman design, a Box-Behnken design was developed for further optimization. A multivariate quadratic regression model was employed to fit the data of the Box-Behnken design and search for the optimum fermentation medium which was as follows (g·L-1): ammonium acetate 9.00, yeast extraction powder 7.00, sodium carboxymethyl cellulose 0.31, beef extract 4.00, NaCl 4.00, K₂HPO₄·3H₂O 0.40, MgSO₄·7H₂O 0.20, CaCl₂ 0.09, FeCl₃ 0.01. The expected desirability values (Dv) with the optimum fermentation medium was 1.892. Five validation experiments were implemented with the optimum fermentation medium and their average Dv was 1.865. The relative error between the experimental values and the expected value was 1.14%, which indicated that the expected value fits experimental values.