|本期目录/Table of Contents|

[1]刘学,薛亚平,柳志强,等.重组青霉素G酰化酶拆分制备(S)-邻氯苯甘氨酸[J].生物加工过程,2013,11(01):5-11.[doi:10.3969/j.issn.1672-3678.2013.01.002]
 LIU Xue,XUE Yaping,LIU Zhiqiang,et al.Preparation of(S)-2-chlorophenyl glycine using penicillin G acylase[J].Chinese Journal of Bioprocess Engineering,2013,11(01):5-11.[doi:10.3969/j.issn.1672-3678.2013.01.002]
点击复制

重组青霉素G酰化酶拆分制备(S)-邻氯苯甘氨酸()
分享到:

《生物加工过程》[ISSN:1672-3678/CN:32-1706/Q]

卷:
11
期数:
2013年01期
页码:
5-11
栏目:
出版日期:
2008-01-30

文章信息/Info

Title:
Preparation of(S)-2-chlorophenyl glycine using penicillin G acylase
文章编号:
1672-3678(2013)01-0005-07
作者:
刘学薛亚平柳志强王亚军郑裕国
浙江工业大学 生物工程研究所 教育部生物转化与生物净化工程研究中心,杭州 310014
Author(s):
LIU XueXUE YapingLIU ZhiqiangWANG YajunZHENG Yuguo
Engineering Research Center of Bioconversion and Biopurification of the Ministry of Education, Institute of Bioengineering,Zhejiang University of Technology,Hangzhou 310014,China
关键词:
青霉素G酰化酶(S)-邻氯苯甘氨酸 拆分 优化
分类号:
O623.736
DOI:
10.3969/j.issn.1672-3678.2013.01.002
文献标志码:
A
摘要:
对产青霉素G酰化酶的重组枯草芽胞杆菌发酵产酶条件进行优化,确定优化后的发酵条件:可溶性淀粉10 g/L、蛋白胨12 g/L、酵母粉3 g/L、NaCl 10 g/L; pH 7.5、培养温度37 ℃、装液量80 mL(500 mL三角瓶)、培养28 h,青霉素G酰化酶的表达水平由最初的7.34 U/mL 提高至18.23 U/mL。以表达青霉素G酰化酶的枯草芽胞杆菌发酵液为酶源,在水相中对映选择性催化N-苯乙酰-(R,S)-邻氯苯甘氨酸制备(S)-邻氯苯甘氨酸,当底物浓度为100 mol/L时转化4 h,转化率达44.2%。对底物浓度为80 mmol/L反应液中的(S)-邻氯苯甘氨酸进行分离,达到理论收率的94.29%(以N-苯乙酰-(R,S)-邻氯苯甘氨酸的0.5倍摩尔量为理论产率),e.e.值大于99.9%。170 ℃条件下,N-苯乙酰-(R)-邻氯苯甘氨酸与苯乙酸共熔消旋为N-苯乙酰-(R,S)-邻氯苯甘氨酸可用于循环拆分。

参考文献/References:

[1] Bousquet A,Muslino A.Hydroxyacetic ester derivatives,preparation method and use as synthesis intermediates:US,6573381B1[P].2003-06-03.
[2] Herbert J M,Savi P,Maffrand J P.Biochemical and pharmacological properties of clopidogrel:a new ADP receptor antagonist[J].Eur Heart J Suppl,1999,1(Sup):31-40.
[3] Campo G,Fileti L,de Cesare N,et al.Long-term clinical outcome based on aspirin and clopidogrel responsiveness status after elective percutaneous coronary intervention[J].J Am College Cardiol,2010,56(18):1447-1455.
[4] 王威,薛亚平,郑裕国.氯吡格雷生产技术研究进展[J].现代化工,2011,31(5):30-34.
[5] Lin S S-S,Chen C C.Process for preparation of 2-chlorophenylglycine derivatives and enantiomerically separation:US,20040176637[P].2004-09-09.
[6] 梁美好,沈正荣.(+)-氯吡格雷的合成工艺改进[J].中国药物化学杂志,2007,17(3):163-165.
[7] 杨华铮,宋洪海.硫酸氢氯吡格雷的制备方法:中国,101121720A[P].2008-02-13.
[8] 沈立新,袁利,刘福双,等.一种新的制备氯吡格雷及其盐的方法:中国,101787032A[P].2010-07-28.
[9] Maheshwari K K,Sarma R K,Joshi S V,et al.Racemization of optically active 2-substituted phebyl glycine esters:US,20040073057[P].2004-04-15.
[10] Battula S R.A process for resolution of methylamino(2-chloprophenyl)acetate:WO,2006003671A1[P].2006-01-12.
[11] 丁桂俐,赵敏,吴范宏,等.邻氯苯甘氨酸甲酯的拆分[J].广州化工,2007,35(6):44-48.
[12] 吴范宏,赵敏,杨雪艳,等.一种S-(+)-邻氯苯甘氨酸甲酯的拆分方法:中国,101497575A[P].2009-08-05.
[13] Katoh O,Uragaki T,Nakamura T.Process for producing optically active α-amino acid and optically active α-amino acid amide:WO,0187819A1[P].2001-11-22.
[14] Asano Y,Inoue A.L-amino acid amide asymmetric hydrolase and encoding the same:EP,1770166 A1[P].2007-04-04.
[15] 舒亮,包志坚,林昌军,等.一种S-(+)-邻氯苯甘氨酸的制备方法:中国,101560533A[P].2009-10-20.
[16] Ferraboschi P,Mieri M D,Galimberti F.Chemo-enzymatic approach to the synthesis of the antithrombotic clopidogrel[J].Tetrahedron:Asymmetry,2010,21:2136-2141.
[17] Hwang S O,Kim K S,Kim Y J.Method for preparing clopidogrel and its derivatives:WO,2009151256 A2[P].2009-12-17.
[18] Fadnavis N W,Devi V A,Jasti L S.Resolution of racemic 2-chlorophenyl glycine with immobilized penicillin G acylase[J].Tetrahedron:Asymmetry,2008,19:2363-2366.
[19] 夏仕文,方国兰.一种制备氯吡格雷手性中间体(S)-邻氯苯甘氨酸甲酯的化学-酶法:中国,101864464A[P].2010-10-20.
[20] Chen C S,Fujimoto Y,Girdaukas G,et al.Quantitative analyses of biochemical kinetic resolutions of enantiomers[J].J Am Chem Soc,1982,104:294-1299
[21] De Leon A,Galindo E,Ramirez O T.A postfermentative stage improves penicillin acylase production by a recombinant E.coli[J].Biotechnol Lett,1996,18(18):927-932.
[22] De Leon A,Hernandez V,Galindo E,et al.Effects of dissolved oxygen tension on the production of recombinant penicillin acylase in Escherichia coli[J].Enzyme Microb Technol,2003,33(5):689-697.

备注/Memo

备注/Memo:
收稿日期:2012-10-29
基金项目:国家重点基础研究发展计划(973计划)资助( 2011CB710804)
作者简介:刘学(1988—),女,安徽合肥人,硕士研究生,研究方向:生物催化与转化; 郑裕国(联系人),教授,E-mail:zhengyg@zjut.edu.cn.
更新日期/Last Update: 2013-01-30