青霉素G酰化酶工业进化的研究进展  

Research progress in the industrial evolution of penicillin G acylase

作　　者：任丽梅 王晓茹 祁永浩 韩广欣 李小兵[1,2,3] REN Limei;WANG Xiaoru;QI Yonghao;HAN Guangxin;LI Xiaobing(Department of Chemical Engineering,Shijiazhuang University,Shijiazhuang 050035,Hebei,China;Hebei Provincial University Microbiology Pharmaceutical Application Technology Research and Development Center,Shijiazhuang University,Shijiazhuang 050035,Hebei,China;Hebei International Joint Research Center for Biopharmaceutical,Shijiazhuang University,Shijiazhuang 050035,Hebei,China)

机构地区：[1]石家庄学院化工学院,河北石家庄050035 [2]石家庄学院河北省高校微生物制药应用技术研发中心,河北石家庄050035 [3]石家庄学院河北省生物制药国际联合研究中心,河北石家庄050035

出　　处：《生物资源》2023年第5期421-430,共10页Biotic Resources

基　　金：河北省高校应用技术研发中心平台项目(2020-4)。

摘　　要：青霉素G酰化酶是近几十年来β内酰胺类抗生素领域应用最广、开发最成功的酶之一。伴随着β-内酰胺类抗生素由化学合成法变更为酶法在中国的大规模产业化,得到了充分的开发与应用,取得了成功。青霉素G酰化酶不但用于水解制备6-APA、7-ADCA,更重要的是用于氨苄西林、头孢氨苄、阿莫西林、头孢拉定、头孢克洛等抗生素的制备。本文综述了近15年青霉素G酰化酶在我国研究与应用的历史沿革、基因与蛋白质结构、工业应用表达体系、工业评价标准与进化研究,还对各种突变株在具体医药工业领域的开发应用进行了综述,旨在梳理青霉素G酰化酶结构与性能的进化趋势以及在医药工业领域取得的巨大成就,同时也为相关人员在此领域进行深耕提供参考。Penicillin G acylase(PGA)is one of the most widely used and successfully developed enzymes in the field of p-lactam antibiotics in recent decades.In China,along with the large-scale industrialization of β-lactam antibiotics,chemical synthesis methods to enzymatic methods,PGA have been fully developed and applied,and achieved success.Penicillin G acylase is not only used for hydrolysis to prepare 6-APA and 7-ADCA,but also for semisynthetic antibiotics such as ampicillin,cephalexin,amoxicillin,cefradine and cefaclor.This paper reviews the history,gene and protein structure,industrial expression system,industrial evaluation criteria and evolution of penicillin G acylase research and application in China in the past 15 years.At the same time,the development and application of various mutants of penicillin G acylase in specific pharmaceutical industry fields are also reviewed,aiming to sort out the evolution trend of the structure and performance of penicillin G acylase,its great achievements in the pharmaceutical industry field,and point out the direction for related researchers to delve deeper in this field.

关 键 词：青霉素G酰化酶 6-APA 抗生素 突变体 进化 

分 类 号：Q814[生物学—生物工程]