扩环酶在头孢菌素类抗生素生产中的应用进展

Application Progress of Expandase in Cephalosporins Production

扩环酶是一类典型的铁(Ⅱ)/2-酮戊二酸依赖性双加氧酶,该酶最主要的特点是能将青霉素的五元四氢噻唑环扩环为六元二氢噻嗪环结构,从而生成头孢菌素。文章阐述了扩环酶的来源,并以来自棒状链霉菌的去乙酰氧基头孢菌素C合酶和来自顶头孢霉的去乙酰头孢菌素C合成/羟化酶作为主要研究对象,详细介绍了扩环酶的结构特性、作用机制及酶修饰工作,总结出对青霉素G扩环效率较好的氨基酸位点突变。此外,由于去乙酰氧基头孢菌素C合酶可以将青霉素N扩环生成去乙酰氧基头孢菌素C,去乙酰头孢菌素C合成/羟化酶可以将青霉素N扩环生成去乙酰头孢菌素C,导致两种扩环酶具有不同的工业用途,因此文章还对当前扩环酶的工业应用进展进行总结,为提高酶法生产头孢菌素类抗生素及其医药中间体的产量提供了现实依据。

Expandase is a typical class of Fe(Ⅱ)/α-ketoglutarate-dependent dioxygenases(α-KGDs).The most important characteristic of this enzyme was that it could be enlarged penicillins five-membered tetrahydrothiazole ring to six-membered dihydrothiazide ring structure to obtain cephalosporins.The origin of expandase was described,which the main research objects were deacetoxycephalosporin C synthase from Streptomyces coryneformis and deacetylcephalosporin C synthesis/hydroxylase from Acremonium chrysogenum.Here,the structural characteristics,mechanism of action as well as enzyme modification of expandase were introduced in detail,which sum up amino acid site mutation for higher efficiency with penicillin N.Beside,because of deacetoxycephalosporin C synthase can synthesize penicillin N into deacetoxycephalosporin C and deacetylcephalosporin C synthesis/hydroxylase can synthesize penicillin N into deacetylcephalosporin C,leaded to different industrial uses for the two kinds of expandase.Hence,this paper summarized the industrial application progress of expandase,which provided realistic basis for enzymatic production cephalosporins and medical intermediate.