| 羰基还原酶不对称还原（R）-6-氰基-5-羟基-3-羰基己酸叔丁酯 |
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| 引用本文： | 曹政,王亚军,肖黎,柳志强,郑裕国.羰基还原酶不对称还原（R）-6-氰基-5-羟基-3-羰基己酸叔丁酯[J].生物加工过程,2013,11(1):17-22. |
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| 作者姓名： | 曹政 王亚军 肖黎 柳志强 郑裕国 |
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| 作者单位： | 浙江工业大学生物工程研究所生物转化与生物净化教育部工程研究中心 |
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| 基金项目： | 国家重点基础研究发展计划(973计划)资助(2011CB710800) |
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| 摘 要： | 选择R-羰基还原酶和葡萄糖脱氢酶双酶，协同催化（R）-6-氰基5-羟基-3-羰基己酸叔丁酯不对称还原制备阿托伐他汀关键手性合成子6-氰基-（3R，5R）-二羟基已酸叔丁酯。转化条件优化结果显示：在不添加外源性辅酶NADP（H）、菌体用量15．0g/L、147．0g/L（R）-6-氰基-5-羟基-3-羰基己酸叔丁酯、128．2g／L葡萄糖，30℃、pH6．5条件下反应6h后，底物转化率达到100％，产物d．e．值大于99．5％。
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| 关 键 词： | 不对称生物还原 阿托伐他汀 6-氰基-（3R，5R）-二羟基己酸叔丁酯 辅酶再生 |
Asymmetric reduction of t-butyl 6-cyano-(5R)-hydroxy-3-carbonylhexanoate by carbonyl reductase |
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| CAO Zheng,WANG Yajun,XIAO Li,LIU Zhiqiang,ZHENG Yuguo.Asymmetric reduction of t-butyl 6-cyano-(5R)-hydroxy-3-carbonylhexanoate by carbonyl reductase[J].Chinese Journal of Bioprocess Engineering,2013,11(1):17-22. |
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| Authors: | CAO Zheng WANG Yajun XIAO Li LIU Zhiqiang ZHENG Yuguo |
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| Institution: | (Engineering Research Center of Bioconversion and Biopurification of the Ministry of Education,Institute of Bioengineering, Zhejiang University of Technology,Hangzhou 310014,China) |
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| Abstract: | t-butyl 6-cyano- （ 3R, 5R） -dihydroxyhexanoate, a key chiral building block for atorvastatin, was synthesized through asymmetric reduction of （R）-6-cyano-5-hydroxy-3-carbonylhexanoate catalyzed by carbonyl reductase coupled with glucose dehydrogenase. The optimized biocatalytic conditions were obtained ： （R） -6-cyano-5-hydroxy-3-carbonylhexanoate 147.0 g/L, glucose 128.2 g/L, cell loading 15.0 g/L, the pH 6.5, and 30 ℃. Under these conditions, （R） -6-cyano-5-hydroxy-3-carbonylhexanoate was completly converted for 6 h. Without exogenous addition of NADP （H） and with t-butyl 6-cyano-（ 3R, 5R）-dihydroxyhexanoate the d. e. value was over 99.5%. |
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| Keywords: | asymmetric bioreduction atorvastatin t-butyl 6-cyano-（ 3R 5R ） -dihydroxyhexanoate coenzyme regeneration |
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