Sio Charles F, Quax Wim J
Pharmaceutical Biology, University Centre for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Curr Opin Biotechnol. 2004 Aug;15(4):349-55. doi: 10.1016/j.copbio.2004.06.006.
Whereas the beta-lactam acylases are traditionally used for the hydrolytic processing of penicillin G and cephalosporin C, new and mutated acylases can be used for the hydrolysis of alternative fermentation products as well as for the synthesis of semisynthetic beta-lactam antibiotics. Three-dimensional structural analyses and site-directed mutagenesis studies have increased the understanding of the catalytic mechanism of these enzymes. The yield of hydrolysis and synthesis has been greatly improved by process design, including immobilization of the enzyme and the use of alternative reaction media. Significant advances have also been made in the resolution of racemic mixtures by means of stereoselective acylation/hydrolysis using beta-lactam acylases.
传统上,β-内酰胺酰基酶用于青霉素G和头孢菌素C的水解处理,而新型和突变的酰基酶可用于替代发酵产物的水解以及半合成β-内酰胺抗生素的合成。三维结构分析和定点诱变研究增进了对这些酶催化机制的理解。通过工艺设计,包括酶的固定化和使用替代反应介质,水解和合成的产率得到了极大提高。利用β-内酰胺酰基酶进行立体选择性酰化/水解拆分外消旋混合物也取得了重大进展。