Optimization of fermentation medium to maximize the production of recombinant human asparaginase in Escherichia coli through the statistical design of experiments

Abstract

Aim: Recombinant human asparaginase (rhASP) from Escherichia coli is an important therapeutic enzyme used in the treatment of malignant cancers. Due to such a pivotal role, rhASP production in E. coli has drawn great attention of the biopharmaceutical market commercially. The present work aims at the optimization of fermentation medium for the production of rhASP in E. coli. Materials and Methods: The rhASP yield is optimized using sequential optimization designs comprising one variable at a time, Taguchi design, and central composite designs (CCDs). Taguchi design is used to select the effective variables such as soytone, sodium pyruvate, trace element solution, vitamin solution, and yeast extract, which are further optimized by CCD under response surface methodology. Results and Discussion: The CCD design developed a quadratic model with high adequacy for the prediction of rhASP yield with a statistically significant response (R2 = 97.49% and P < 0.0001) toward the variables. Conclusion: The CCD results showed that the maximum rhASP yield of 38.4387 μg/mL was achieved with the optimized concentrations of media components comprising 9.0 g/L of soytone, 7.5 g/L of sodium pyruvate, 12.5 mL/L of trace element solution, 12.5 mL/L of vitamin solution, and 9.0 g/L of yeast extract.