Evaluation of Packed-Bed Reactor and Continuous Stirred Tank Reactor for the Production of Colchicine Derivatives

Abstract

Bioconversion of colchicine into its pharmacologically active derivative 3-demethylated colchicine (3-DMC) mediated by P450BM3 enzyme is an economic and promising strategy for the production of this inexpensive and potent anticancer drug. Continuous stirred tank reactor (CSTR) and packed-bed reactor (PBR) of 3 L and 2 L total volumes were compared for the production of 3-demethylated colchicine (3-DMC) a colchicine derivative using Bacillus megaterium MTCC*420 under aerobic conditions. Statistical optimization technique was utilized with the most significant variables, that is, dissolved oxygen (DO), colchicine concentration, and process time for optimization. The validation of the model was performed by experiments on the predicted values in an individual run, and the optimum parameters were DO (~50%), colchicine concentration (7.5 g/L), and process time (39 h) resulted in a maximum bioconversion of 3-DMC 3.36 g/L. The PBR reactor achieved much higher productivity (6.58 g/L/h) as reported by earlier researchers. This is the first report on the use of PBR for bioconversion of colchicine.