青霉素酰化酶促合成β-内酰胺抗生素的过程优化研究进展

Progress in optimization for synthesis of β-lactam antibiotics with penicillin acylase

β-内酰胺抗生素是临床引用中最为广泛的一类抗生素,其生产正经历由化学合成到生物催化的转变。青霉素酰化酶是半合抗工业中最重要的一类酶,近年来广泛应用于β-内酰胺抗生素合成的研究中。相对热力学控制而言,动力学控制合成是更受青睐。酶促合成过程中的反应条件的优化控制尤为重要,包括pH、温度、底物浓度和底物比等影响因素的选择对于不同来源的酶和不同目的抗生素不尽相同。反应条件优化以及反应器的合理设计可以提高产物的收率并有效降低成本,是合成β-内酰胺抗生素新的研究热点。本文针对各反应因素以及反应器设计进行综述,并指出未来的可能研究方向。

The manufacture of β-1actam antibiotics is experiencing a transfer from chemical synthesis to enzymatic ones because the latter has the advantages such as mild operational conditions and no waste production. As the most important enzyme in the β-1actam antibiotics production, penicillin acylase was applied in the synthesis of clinical penicillins and cephalosporins. Compared to thermodynamically controlled synthesis, kinetically controlled synthesis is more interesting due to the high yield can be obtained by optimization of the reaction conditions and design of bioreactor. The optimization of operational conditions such as pH, temperature, substrate concentration and ratio of substrate in kinetic synthesis were discussed in detail. One-pot synthesis and design of bioreactor were also reviewed. The future research was proposed in this review.