|本期目录/Table of Contents|

[1]刘艳** 裴小琼 崔璨 丁照云 吴中柳.[综 述] 生物催化不对称还原制备(R)-1-[3,5-二(三氟甲基)苯基]乙醇研究进展[J].应用与环境生物学报,2020,26(04):1-13.[doi:10.19675/j.cnki.1006-687x.2019.10019]
 LIU Yan **,PEI Xiaoqiong,CUI Can,et al.Advances in (R)-1-[3,5-bis(trifluoromethyl)phenyl] ethanol production via biocatalytic asymmetric reduction[J].Chinese Journal of Applied & Environmental Biology,2020,26(04):1-13.[doi:10.19675/j.cnki.1006-687x.2019.10019]
点击复制

[综 述] 生物催化不对称还原制备(R)-1-[3,5-二(三氟甲基)苯基]乙醇研究进展()
分享到:

《应用与环境生物学报》[ISSN:1006-687X/CN:51-1482/Q]

卷:
26卷
期数:
2020年04期
页码:
1-13
栏目:
综 述
出版日期:
2020-08-25

文章信息/Info

Title:
Advances in (R)-1-[3,5-bis(trifluoromethyl)phenyl] ethanol production via biocatalytic asymmetric reduction
作者:
刘艳1** 裴小琼1 崔璨12 丁照云12 吴中柳1
1中国科学院成都生物研究所,中国科学院环境与应用微生物重点实验室,环境微生物四川省重点实验室 成都 610041
2中国科学院大学 北京 100049
Author(s):
LIU Yan1 ** PEI Xiaoqiong1 CUI Can1 2 Ding Zhaoyun1 2 & WU Zhongliu 1
1 Key Laboratory of Environmental and Applied Microbiology & Environmental Microbiology Key Laboratory of Sichuan Province , Chengdu Institute of Biology, Chinese Academy of Sciences , Chengdu 610041, China 2
 University of Chinese Academy of Sciences, Beijing 100049, China
关键词:
羰基还原酶酮还原酶阿瑞匹坦反-Prelog规则手性醇定向进化
Keywords:
carbonyl reductases ketone reductaseAprepitant anti-Prelog rule chiral alcohol directed evolution
DOI:
10.19675/j.cnki.1006-687x.2019.10019
摘要:
(R)-1-[3,5-二(三氟甲基)苯基]乙醇是合成药物阿瑞匹坦的关键中间体. 以羰基还原酶生物催化前手性酮3,5-二(三氟甲基)苯乙酮的方法制备该中间体具有立体选择性优异、反应条件温和、对环境友好等优点,近年来受到广泛关注,目前已报道的高立体选择性酶源(产物ee > 99%)有10余种. 其中原始菌株生物催化体系能够转化底物的浓度普遍低于200 mmol/L,而利用重组Escherichia coli全细胞或者粗酶液则可催化1 mol/L以上的底物. 通过添加离子液体、深共熔溶剂等辅溶剂,羰基还原酶与葡萄糖脱氢酶融合表达以及酶固定化技术等方法优化反应体系可以有效提高底物转化效率. 有些羰基还原酶,如LXCAR、KR01、ChKRED20等,能够催化异丙醇脱氢实现辅酶自循环,其催化体系具有明显优势. 未来利用蛋白质工程技术对野生型的潜力酶进行人工进化,可以进一步提高利于工业应用的酶学性能,同时稳定的生产工艺、规模放大、后处理等方面也需要深入开展研究.(图2 表3 参52)
Abstract:
(R)-1-[3,5-bis(trifluoromethyl)phenyl] ethanol [(R)-1b] is a key intermediate for the synthesis of the chiral drug Aprepitant. Asymmetric reduction of prochiral 1-[3,5-bis(trifluoromethyl)phenyl] ethanone ( 1a) by carbonyl reductases is an efficient and powerful way to produce highly optically active (R)-1b, which has attracted extensive attention in recent years due to its excellent stereoselectivity, mild reaction conditions and environmental friendliness. At present, more than 10 strains and ketoreductases (carbonyl reductases) with excellent (R)-stereoselectity to substrate 1a ( ee > 99%) have been screened from environmental soils or gene databases. When the whole cells of the isolated strains were applied to reduce 1a , the concentrations of transformed substrates were generally lower than 200 mM. However, the whole cells of recombinant Escherichia coli or cell-free enzymes could catalyze higher concentration of substrates up to 1 M. Several methods have been used to improve the catalytic efficiency, such as adding cosolvents (ionic liquids, deep eutectic solvent, etc), co-expression with glucose dehydrogenase and immobilization technology. Ketoreductases such as LXCAR, KR01 and ChKRED20, which can regenerate coenzymes NAD(P)H with isopropanol, have obvious advantages in the production of (R)-1b. In the future, molecule evolution of these potential enzymes using protein engineering technology to improve their performances for industrial applications, stable process, large-scale production as well as post-treatment also need to be further studied.

相似文献/References:

[1]邢晔,刘艳,张超,等.中国白酒酿造物料中分离的酵母菌株在不对称羰基还原中的应用[J].应用与环境生物学报,2013,19(06):1014.[doi:10.3724/SP.J.1145.2013.01014]
 XING Ye,LIU Yan,ZHANG Chao,et al.Asymmetric Ketone Reduction Using Targeted Yeast Collections Isolated from Chinese Liquor Pits[J].Chinese Journal of Applied & Environmental Biology,2013,19(04):1014.[doi:10.3724/SP.J.1145.2013.01014]

备注/Memo

备注/Memo:
收稿日期 Received: 2019-10-14 接受日期 Accepted: 2019-11-27
*国家自然科学基金项目(21708038)资助 Supported by the National Natural Science Foundation of China (21708038)
**通讯作者 Corresponding author (E-mail: liuyan@cib.ac.cn)
点击摘要页题目后的“PDF”可下载阅读全文;本文为已录用的作者修定稿,尚未经编辑全面修改。
引用本文请注明出处本刊;发表刊期和页码将以正式出版时的安排为准,但DOI确定不变。
更新日期/Last Update: 2019-12-05