Response Surface Methodology Optimization of Thebaine Biotransformation into Codeine and Morphine Using Bacillus sp. FAR

Background: Codeine and morphine are important pharmaceuticals having analgesic characteristics. Aim: The current study used response surface methodology to optimize the biotransformation of thebaine into codeine and morphine using Bacillus sp. FAR. Methods: A central composite design was used to determine the optimal concentrations of buffer and thebaine, pH, time, temperature, and biomass. Improvement in transformation was monitored using HPLC-DAD. Results: The optimized conditions employed were pH 7.7 at 36°C for 30 h using a thebaine concentration of 80 μg/mL, 45 mM tris of buffer and 2.9% w/v biomass. The optimal conditions for codeine and morphine production were 2.995 and 1.113 μg, respectively. Conclusion: Optimization demonstrated that pH and biomass had the strongest effects on biotransformation.