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Enhanced enzymatic synthesis of amoxicillin by addition of organic cosolvents with response surface methodology

Xiao-Yun Zhang, Xiang-YuWang, Xiao-Ping Jiang, Shun-Yi Fan, Ye-Wang Zhang

Penicillin acylase (PA) from Kluyvera citrophila was employed for the synthesis of amoxicillin under kinetic control. Twelve organic cosolvents were investigated as additives for enzymatic synthesis of amoxicillin. It indicated that the reaction rate decreased with the increase of solventÂ’s LogP. Ethylene glycol was found to be the suitable additive due to its enhancement of activity of PAand improvement of amoxicillin yield. Then reaction conditions including ethylene glycol concentration, pH, temperature, and substrate concentration were studied. Finally, a response surface methodology (RSM) was employed to obtain the optimal reaction conditions. The model showed that the interaction between temperature, 6-aminopenicillanic acid (6-APA) concentration and themolar ratio of acyl donor to 6-APAwere significant. The highest yield of 92.4%was achieved at the optimal conditions: 116 mmol l-1 of 6-APA, 15 oC and the molar ratio of acyl donor to 6-APAwas 3.4.