Statistical Optimization of Anti-leukemic Enzyme L-Asparaginase Production by Penicillium cyclopium

A sequential optimization strategy, based on statistical experimental designs is employed to enhance L-Asparaginase production. First, a 2-level Plackett-Burman design was applied for bioprocess parameters screen that significantly influence the enzyme production. Seven culture ingredients and fermentation period were examined for their significance on enzyme production and specific activity using Plackett– Burman factorial design. MgSO₄. 7H₂O, KCl and (NH₄)₂SO₄ were the most significant factors improving enzyme production process. The second optimization step was performed using fractional factorial design in order to optimize the amounts of highest positive variables had significant effect on enzyme activity. The second optimization step was to identify optimal values of the three factors that bringing about maximum L-asparaginase activity, using central composite designed experiments. The different media components were initially optimized using the conventional one-factor-at-a time method. Lasparaginase activity in the optimized medium was 160 IU mL⁻¹ which increased 1.54-fold over that of the conventional one-factor-at-a time method basal medium (104.5±1.6 IU mL⁻¹).