文献类型：期刊文献

中文题名：毕赤酵母不对称合成阿托伐他汀中间体

英文题名：Asymmetric synthesis of atorvastatin intermediate by Pichia pastoris X-33

作者：周剑平[1];任宇红[1];张敏洁[1];孙晓锋[1];魏东芝[1]

机构：[1]华东理工大学生物反应器工程国家重点实验室,上海200237

年份：2011

卷号：27

期号：4

起止页码：579

中文期刊名：生物工程学报

外文期刊名：Chinese Journal of Biotechnology

收录：MEDLINE(收录号：21847992);CSTPCD;;Scopus;北大核心:【北大核心2008】；CSCD:【CSCD2011_2012】；PubMed;

基金："十一五"国家科技支撑计划(No.2008BAI63B07)资助~~

语种：中文

中文关键词：毕赤酵母;不对称还原;5-邻苯二甲酰亚胺-3-氧代戊酸乙酯;(R)-3-羟基-5-邻苯二甲酰亚胺基戊酸乙酯

外文关键词：Pichia pastoris X-33; asymmetric reduction; ethyl 5-（1; 3-dioxoisoindolin-2-yl）-3-oxopentanoate; ethyl（R）-3-hydroxy-5-（1; 3-dioxoisoindolin-2-yl）-pentanoate

摘要：阿托伐他汀可通过抑制HMG-CoA还原酶与底物的结合来抑制胆固醇的合成,而(R)-3-羟基-5-邻苯二甲酰亚胺基戊酸乙酯是阿托伐他汀合成的重要中间体。通过对实验室保藏菌种进行筛选,得到一株巴氏毕赤酵母X-33可将5-邻苯二甲酰亚胺-3-氧代戊酸乙酯还原为(R)-3-羟基-5-邻苯二甲酰亚胺基戊酸乙酯。在磷酸盐缓冲液体系中考察了初始底物浓度、反应时间、辅助底物、葡萄糖添加量、pH、温度等因素对产物收率和对映体选择性的影响,获得了较佳的反应条件。选择底物投料量为7 g/L时,当菌体浓度120 g/L,葡萄糖添加量120 g/L,pH 6.5,温度35℃,反应时间12 h,产物(R)-3-羟基-5-邻苯二甲酰亚胺基戊酸乙酯的收率可达到93.12%,对映体过量值可达到98.55%。
Ethyl（R）-3-hydroxy-5-（1,3-dioxoisoindolin-2-yl）-pentanoate is a potential intermediate for the synthesis of HMG-CoA reductase inhibitor（atorvastatin） that can lower the cholesterol level in human blood.In this study,in order to synthesize ethyl（R）-3-hydroxy-5-（1,3-dioxoisoindolin-2-yl）-pentanoate by bioreduction,the yeast strains in our lab were screened.Ethyl（R）-3-hydroxy-5-（1,3-dioxoisoindolin-2-yl）-pentanoate was found to be produced efficiently from ethyl 5-（1,3-dioxoisoindolin-2-yl）-3-oxopentanoate by Pichia pastoris X-33.The effects of initial substrate concentration,reaction time,co-substrate,amount of yeast cells,pH,as well as the temperature on the yield and enantiomeric excesses（e.e.value） of product were examined in mono-phase system.The optimal reaction conditions are as fallows： substrate concentration 7 g/L,cell concentration 120 g/L,glucose concentration 120 g/L,pH 6.5,temperature 35 °C,reaction time 12 h,and the yield 93.12% with the high e.e.value of 98.55%.