Progress in One-pot Bioconversion of Cephalosporin C to 7-Aminocephalosporanic Acid.
Progress in One-pot Bioconversion of Cephalosporin C to 7-Aminocephalosporanic Acid.
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DOI：
10.2174/1389201019666180509093956
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发表时间：
2018-05
影响因子：
2.8
通讯作者：
Q. Tan;J. Qiu;Xiang Luo;Yewang Zhang;Yuting Liu;Yuquan Chen;Jing Yuan;W. Liao
中科院分区：
文献类型：
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作者：
Q. Tan;J. Qiu;Xiang Luo;Yewang Zhang;Yuting Liu;Yuquan Chen;Jing Yuan;W. Liao
研究背景头孢菌素类抗生素是应用最广泛的半合成抗生素，作用于细菌细胞壁(肽聚糖)的合成。临床上生产头孢菌素的关键中间体是7-氨基头孢烷酸(7-ACA)，它是由天然抗生素头孢菌素C(CPC)化学或酶促脱酰而成的。由于化学过程要求苛刻的条件，并释放有毒废物，因此酶促脱酰过程已经取代了化学脱酰过程。方法采用D-氨基酸氧化酶和7-β-(4-羧基丁氨基)-头孢烷酸酰化酶两步法连续两步反应，工业化生产7-氨基头孢烷酸。结果采用单酶法(应用头孢菌素C酰化酶或GLA变异体)、双酶法(DAAO和GLA同时作用)或三酶法(DAAO、GLA和过氧化氢酶同时作用)直接转化CPC合成7-ACA，简化了工艺过程，降低了成本。结论在这里，我们主要集中描述这些一锅法的酶过程，并重点介绍所涉及的生物催化剂的制备。
BACKGROUND Cephalosporins are the most widely used semisynthetic antibiotics, which acted on bacterial cell wall (peptidoglycan) synthesis. The key intermediate for fabricating about twothirds of cephalosporins in clinical use is 7-aminocephalosporanic acid (7-ACA), which is derived from chemical or enzymatic deacylation of the natural antibiotic cephalosporin C (CPC). The chemical deacylation process has been replaced by the enzymatic deacylation process because the chemical process required harsh conditions and released toxic waste. METHODS A two-step enzymatic process that utilized D-amino acid oxidase (DAAO) and 7-β-(4carboxybutanamido)-cephalosporanic acid acylase (GLA) for two successive reactions has been applied for the conversion of CPC to 7-ACA in an industrial scale. RESULTS To simplify the process and lower costs, the one-pot enzymatic processes were developed by the application of the mono-enzymatic process (application of cephalosporin C acylase or the variants of GLA), di-enzymatic process (simultaneous action of DAAO and GLA) or the tri-enzymatic process (simultaneous action of DAAO, GLA and catalase) for direct conversion of CPC to 7-ACA. CONCLUSION Here, we mainly focused on the description of these one-pot enzymatic processes and emphasized on the preparation of the involved biocatalysts.