Enhanced extraction of 3-demethylated colchicine from fermentation broth of Bacillus megaterium: Optimization of process parameters by statistical experimental design

Abstract

Biotransformation of colchicine into its pharmacologically active regiospecific derivative 3-demethylated colchicine (3-DMC) mediated by microbial monooxygenases is an economic and promising strategy for the production of this inexpensive and potent anti-cancer drug. Response surface methodology (RSM), with central composite design (CCD) model, was employed with three extraction variables (temperature, pH, and process time) for optimization; which most significantly affected recovery of 3-DMC. The validity of the model was ascertained by running the predicted values in an individual run; and the optimum parameters, temperature (50°C), pH (10), and process time (120min) resulted in a maximum recovery of 3-DMC 4128mg/L when chloroform (1% v/v) was used as an extraction solvent. RSM in our experiments showed to be a good tool for the extraction of 3-DMC from the fermentation medium. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.