Statistical optimization of process variables for the production of an anticancer drug (colchicine derivatives) through fermentation: at scale-up level.

Effect of various nutritional components and fermentation parameters on biotransformation of colchicine using Bacillus megaterium ACBT03 to produce 3-demethylated colchicine (3-DMC) has been investigated. Initially, Plackett-Burman (PB) design was used to evaluate the 11 nutritional variables to screen medium component that significantly influences the 3-demethylated colchicine (3-DMC) production. Three most statistically significant nutrients that is starch, glycerol and yeast extract were identified. Response surface methodology was used to optimize fermenter operational factors pH, temperature, impeller tip velocity and aeration rate for high 3-DMC production. The predicted results of 3-DMC yield (7689.13mg/l) were obtained at 5-l-jar fermenter after optimization of pH 6.8, temperature 28°C, impeller tip velocity 4650cm/min, and aeration rate 2.0vvm. The validity of model was confirmed; and the optimum medium designed led a maximum 3-DMC yield of 7335mg/l, which had 3-4% variation with predicted results. Furthermore, the experiment was scaled up in the 70-l fermenter.