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1. 发明授权

US07915022B2 Carbonyl reductase, gene thereof and method of using the same 有权
标题翻译：羰基还原酶，其基因及其使用方法
公开(公告)号：US07915022B2
公开(公告)日：2011-03-29
申请号：US12840026
申请日：2010-07-20
申请人： Noriyuki Kizaki , Miho Yano , Masashiro Funaki , Teruaki Takesue , Yoshihiko Yasohara , Souichi Morikawa , Takahisa Nakai , Michihiko Kataoka , Sakayu Shimizu
发明人： Noriyuki Kizaki , Miho Yano , Masashiro Funaki , Teruaki Takesue , Yoshihiko Yasohara , Souichi Morikawa , Takahisa Nakai , Michihiko Kataoka , Sakayu Shimizu
IPC分类号： C12N9/02 , C07K14/00 , C12P21/00 , C12P7/16 , C12P7/02 , C12Q1/26
CPC分类号： C12P13/02 , C12N9/0006 , C12P41/002
摘要： The present invention relates to a polypeptide having an activity to asymmetrically reduce (3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanone to produce (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol isolated from a microorganism belonging to the genus Ogataea, a DNA encoding the polypeptide and a transformant that produces the polypeptide. The present invention moreover relates to a method of producing (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol utilizing the polypeptide or the transformant.Using the polypeptide or transformant of the present invention, optically active alcohols such as (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol and the like can be produced efficiently.
摘要翻译：本发明涉及具有不对称降低（3S）-1-氯-3-叔丁氧基羰基氨基-4-苯基-2-丁酮的活性以产生（2R，3S）-1-氯-3-叔丁氧基羰基氨基-4- 从属于Ogataea的微生物分离的丁氧基羰基氨基-4-苯基-2-丁醇，编码多肽的DNA和产生多肽的转化体。本发明还涉及利用多肽或转化体制备（2R，3S）-1-氯-3-叔丁氧基羰基氨基-4-苯基-2-丁醇的方法。使用本发明的多肽或转化体，可以有效地制备光学活性醇如（2R，3S）-1-氯-3-叔丁氧基羰基氨基-4-苯基-2-丁醇等。

2. 发明授权

US07794993B2 Carbonyl reductase, gene thereof and method of using the same 有权
标题翻译：羰基还原酶，其基因及其使用方法
公开(公告)号：US07794993B2
公开(公告)日：2010-09-14
申请号：US11659481
申请日：2005-08-01
申请人： Noriyuki Kizaki , Miho Yano , Masahiro Funaki , Teruaki Takesue , Yoshihiko Yasohara , Souichi Morikawa , Takahisa Nakai , Michihiko Kataoka , Sakayu Shimizu
发明人： Noriyuki Kizaki , Miho Yano , Masahiro Funaki , Teruaki Takesue , Yoshihiko Yasohara , Souichi Morikawa , Takahisa Nakai , Michihiko Kataoka , Sakayu Shimizu
IPC分类号： C07H21/00 , C12N15/00 , C12N5/10 , C12N1/21 , C12P7/16 , C12P21/00 , C12N9/02 , C07K14/00
CPC分类号： C12P13/02 , C12N9/0006 , C12P41/002
摘要： The present invention relates to a polypeptide having an activity to asymmetrically reduce (3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanone to produce (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol isolated from a microorganism belonging to the genus Ogataea, a DNA encoding the polypeptide and a transformant that produces the polypeptide. The present invention moreover relates to a method of producing (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol utilizing the polypeptide or the transformant. Using the polypeptide or transformant of the present invention, optically active alcohols such as (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol and the like can be produced efficiently.
摘要翻译：本发明涉及具有不对称还原（3S）-1-氯-3-叔丁氧基羰基氨基-4-苯基-2-丁酮的活性以产生（2R，3S）-1-氯-3-叔丁氧基羰基氨基-4- 从属于Ogataea的微生物分离的丁氧基羰基氨基-4-苯基-2-丁醇，编码多肽的DNA和产生多肽的转化体。本发明还涉及利用多肽或转化体制备（2R，3S）-1-氯-3-叔丁氧基羰基氨基-4-苯基-2-丁醇的方法。使用本发明的多肽或转化体，可以有效地制备光学活性醇如（2R，3S）-1-氯-3-叔丁氧基羰基氨基-4-苯基-2-丁醇等。

3. 发明申请

US20080261281A1 Novel Carbonyl Reductase, Gene Thereof and Method of Using the Same 有权
标题翻译：新型羰基还原酶，其基因及其使用方法
公开(公告)号：US20080261281A1
公开(公告)日：2008-10-23
申请号：US11659481
申请日：2005-08-01
申请人： Noriyuki Kizaki , Miho Yano , Masahiro Funaki , Teruaki Takesue , Yoshihiko Yasohara , Souichi Morikawa , Takahisa Nakai , Michihiko Kataoka , Sakayu Shimizu
发明人： Noriyuki Kizaki , Miho Yano , Masahiro Funaki , Teruaki Takesue , Yoshihiko Yasohara , Souichi Morikawa , Takahisa Nakai , Michihiko Kataoka , Sakayu Shimizu
IPC分类号： C12N9/14 , C12N15/52 , C12N1/21 , C12P13/02
CPC分类号： C12P13/02 , C12N9/0006 , C12P41/002
摘要： The present invention relates to a polypeptide having an activity to asymmetrically reduce (3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanone to produce (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol isolated from a microorganism belonging to the genus Ogataea, a DNA encoding the polypeptide and a transformant that produces the polypeptide. The present invention moreover relates to a method of producing (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol utilizing the polypeptide or the transformant.Using the polypeptide or transformant of the present invention, optically active alcohols such as (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol and the like can be produced efficiently.
摘要翻译：本发明涉及具有不对称还原（3S）-1-氯-3-叔丁氧基羰基氨基-4-苯基-2-丁酮的活性以产生（2R，3S）-1-氯-3-叔丁氧基羰基氨基-4- 从属于Ogataea的微生物分离的丁氧基羰基氨基-4-苯基-2-丁醇，编码多肽的DNA和产生多肽的转化体。本发明还涉及利用多肽或转化体制备（2R，3S）-1-氯-3-叔丁氧基羰基氨基-4-苯基-2-丁醇的方法。使用本发明的多肽或转化体，可以有效地制备光学活性醇如（2R，3S）-1-氯-3-叔丁氧基羰基氨基-4-苯基-2-丁醇等。

4. 发明授权

US06218156B1 Gene encoding carbonyl reductase, and methods for its use 有权
标题翻译：基因编码羰基还原酶及其使用方法
公开(公告)号：US06218156B1
公开(公告)日：2001-04-17
申请号：US09367012
申请日：1999-11-24
申请人： Yoshihiko Yasohara , Noriyuki Kizaki , Junzo Hasegawa , Masaru Wada , Sakayu Shimizu , Michihiko Kataoka , Kazuhiko Yamamoto , Hiroshi Kawabata , Keiko Kita
发明人： Yoshihiko Yasohara , Noriyuki Kizaki , Junzo Hasegawa , Masaru Wada , Sakayu Shimizu , Michihiko Kataoka , Kazuhiko Yamamoto , Hiroshi Kawabata , Keiko Kita
IPC分类号： C12P762
CPC分类号： C12P7/62 , C12N9/0006 , C12P41/002
摘要： An enzyme having carbonyl reduction activity of reducing a carbonyl compound asymmetrically to produce an optically active alcohol, a DNA coding the enzyme, a plasmid having the DNA, a transformant which is a cell transformed with the plasmid, and a production method of an optically active alcohol using the enzyme and/or the transformed cell are provided.
摘要翻译：具有不对称还原羰基化合物以产生光学活性醇的羰基还原活性的酶，编码该酶的DNA，具有该DNA的质粒，作为用该质粒转化的细胞的转化体的转化体和光学活性物质的制备方法提供使用酶和/或转化细胞的醇。

5. 发明授权

US06448052B2 Carbonyl reductase enzyme and methods for its use 有权
标题翻译：羰基还原酶及其使用方法
公开(公告)号：US06448052B2
公开(公告)日：2002-09-10
申请号：US09777157
申请日：2001-02-05
申请人： Yoshihiko Yasohara , Noriyuki Kizaki , Junzo Hasegawa , Masaru Wada , Sakayu Shimizu , Michihiko Kataoka , Kazuhiko Yamamoto , Hiroshi Kawabata , Keiko Kita
发明人： Yoshihiko Yasohara , Noriyuki Kizaki , Junzo Hasegawa , Masaru Wada , Sakayu Shimizu , Michihiko Kataoka , Kazuhiko Yamamoto , Hiroshi Kawabata , Keiko Kita
IPC分类号： C12P762
CPC分类号： C12P7/62 , C12N9/0006 , C12P41/002
摘要： An enzyme having carbonyl reduction activity of reducing a carbonyl compound asymmetrically to produce an optically active alcohol, a DNA coding the enzyme, a plasmid having the DNA, a transformant which is a cell transformed with the plasmid, and a production method of an optically active alcohol using the enzyme and/or the transformed cell are provided.
摘要翻译：具有不对称还原羰基化合物以产生光学活性醇的羰基还原活性的酶，编码该酶的DNA，具有该DNA的质粒，作为用该质粒转化的细胞的转化体的转化体和光学活性物质的制备方法提供使用酶和/或转化细胞的醇。

6. 发明申请

US20060223152A1 Optically active 2-allylcarboxylic acid derivative and process for producing the same 失效
标题翻译：光学活性2-烯丙基羧酸衍生物及其制备方法
公开(公告)号：US20060223152A1
公开(公告)日：2006-10-05
申请号：US10553394
申请日：2004-04-16
申请人： Kazumi Okuro , Susumu Amano , Noriyuki Kizaki , Teruaki Takesue , Masaru Mitsuda , Noriyuki Ito , Yoshihiko Yasohara
发明人： Kazumi Okuro , Susumu Amano , Noriyuki Kizaki , Teruaki Takesue , Masaru Mitsuda , Noriyuki Ito , Yoshihiko Yasohara
IPC分类号： C12P13/00 , C07F3/02
CPC分类号： C07C233/18 , C07B2200/07 , C07C51/06 , C07C67/20 , C07C233/05 , C07C271/64 , C12P7/40 , C12P41/005 , C07C57/03 , C07C69/533
摘要： The present invention provides a process for producing an optically active 2-allylcarboxylic acid derivative, which is useful as a pharmaceutical intermediate, from readily available and inexpensive starting materials by the process which can be practiced on a commercial scale in a simple and easy manner, and certain 2-allylcarboxamide derivatives, which are novel and important intermediates in that process. An N-allylcarboxamide derivative undergoes rearrangement reaction diastereoselectively in the presence of a base to give a 2-allylcarboxamide derivative, the resulting derivative is subjected to a carbamation reaction and solvolysis to give an optically active 2-allylcarboxylic acid ester, and then the ester obtained is stereoselectively hydrolyzed using an enzyme to produce 2-allylcarboxylic acid having a high optical purity. In addition, the present invention provides a 2-allylcarboxamide derivative compound which is a novel intermediate in the process of the present invention.
摘要翻译：本发明提供了一种用于制备可用作药物中间体的光学活性2-烯丙基羧酸衍生物的方法，其由易于获得且廉价的原料通过可以简单和容易的方式在商业规模上实施的方法制备，和某些2-烯丙基羧酰胺衍生物，它们是该方法中新颖且重要的中间体。 N-烯丙基甲酰胺衍生物在碱存在下非对映选择性地进行重排反应，得到2-烯丙基甲酰胺衍生物，所得衍生物进行氨基甲酰化反应和溶剂解，得到光学活性2-烯丙基羧酸酯，然后得到所述酯使用酶进行立体选择性水解以产生具有高光学纯度的2-烯丙基羧酸。此外，本发明提供了在本发明的方法中是新型中间体的2-烯丙基甲酰胺衍生物化合物。

7. 发明授权

US07282605B2 Optically active 2-allylcarboxylic acid derivative and process for producing the same 失效
标题翻译：光学活性2-烯丙基羧酸衍生物及其制备方法
公开(公告)号：US07282605B2
公开(公告)日：2007-10-16
申请号：US10553394
申请日：2004-04-16
申请人： Kazumi Okuro , Susumu Amano , Noriyuki Kizaki , Teruaki Takesue , Masaru Mitsuda , Noriyuki Ito , Yoshihiko Yasohara
发明人： Kazumi Okuro , Susumu Amano , Noriyuki Kizaki , Teruaki Takesue , Masaru Mitsuda , Noriyuki Ito , Yoshihiko Yasohara
IPC分类号： C07C291/00 , C07C237/16 , C07C237/18 , C07C237/20
CPC分类号： C07C233/18 , C07B2200/07 , C07C51/06 , C07C67/20 , C07C233/05 , C07C271/64 , C12P7/40 , C12P41/005 , C07C57/03 , C07C69/533
摘要： The present invention provides a process for producing an optically active 2-allylcarboxylic acid derivative, which is useful as a pharmaceutical intermediate, from readily available and inexpensive starting materials by the process which can be practiced on a commercial scale in a simple and easy manner, and certain 2-allylcarboxamide derivatives, which are novel and important intermediates in that process.An N-allylcarboxamide derivative undergoes rearrangement reaction diastereoselectively in the presence of a base to give a 2-allylcarboxamide derivative, the resulting derivative is subjected to a carbamation reaction and solvolysis to give an optically active 2-allylcarboxylic acid ester, and then the ester obtained is stereoselectively hydrolyzed using an enzyme to produce 2-allylcarboxylic acid having a high optical purity. In addition, the present invention provides a 2-allylcarboxamide derivative compound which is a novel intermediate in the process of the present invention.
摘要翻译：本发明提供了一种用于制备可用作药物中间体的光学活性2-烯丙基羧酸衍生物的方法，其由易于获得且廉价的原料通过可以简单和容易的方式在商业规模上实施的方法制备，和某些2-烯丙基羧酰胺衍生物，它们是该方法中新颖且重要的中间体。 N-烯丙基甲酰胺衍生物在碱存在下非对映选择性地进行重排反应，得到2-烯丙基甲酰胺衍生物，所得衍生物进行氨基甲酰化反应和溶剂解，得到光学活性2-烯丙基羧酸酯，然后得到所述酯使用酶进行立体选择性水解以产生具有高光学纯度的2-烯丙基羧酸。此外，本发明提供了在本发明的方法中是新型中间体的2-烯丙基甲酰胺衍生物化合物。

8. 发明申请

US20090104671A1 METHOD FOR PRODUCING OPTICALLY ACTIVE 2-(N-SUBSTITUTED AMINOMETHYL)-3-HYDROXYBUTYRIC ACID ESTER 审中-公开
标题翻译：生产光学活性2-（N-取代氨基甲酰基）-3-羟基丁酸的方法
公开(公告)号：US20090104671A1
公开(公告)日：2009-04-23
申请号：US11996271
申请日：2006-07-19
申请人： Yoshihiko Yasohara , Miho Yano , Shigeru Kawano , Noriyuki Kizaki
发明人： Yoshihiko Yasohara , Miho Yano , Shigeru Kawano , Noriyuki Kizaki
IPC分类号： C12P13/02 , C12P17/10 , C12P13/00
CPC分类号： C12P13/02 , C12P17/10
摘要： The present invention relates to a method for producing optically active 2-(N-substituted aminomethyl)-3-hydroxybutyric acid esters wherein a 2-(N-substituted aminomethyl)-3-oxobutyric acid ester is treated with an enzyme source capable of stereoselectively reducing said ester to the corresponding optically active 2-(N-substituted aminomethyl)-3-hydroxybutyric acid ester having the (2S,3R) configuration. The present invention provides an efficient method for industrially producing optically active 2-(N-substituted aminomethyl)-3-hydroxybutyric acid esters, in particular such compounds having the (2S,3R) configuration, which are useful as intermediates for the production of medicinal compounds, among others.
摘要翻译：本发明涉及一种光学活性2-（N-取代氨基甲基）-3-羟基丁酸酯的制备方法，其中2-（N-取代氨基甲基）-3-氧代丁酸酯可用立体选择性的酶源处理将所述酯还原成具有（2S，3R）构型的相应的光学活性2-（N-取代氨基甲基）-3-羟基丁酸酯。本发明提供了工业上制造光学活性2-（N-取代氨基甲基）-3-羟基丁酸酯的有效方法，特别是具有（2S，3R）构型的这种化合物，其可用作生产药物的中间体化合物等。

9. 发明授权

US08008461B2 Carbonyl reductase, gene therefor and use thereof 失效
标题翻译：羰基还原酶，其基因及其用途
公开(公告)号：US08008461B2
公开(公告)日：2011-08-30
申请号：US11665065
申请日：2005-10-20
申请人： Noriyuki Kizaki , Makoto Ueda , Daisuke Moriyama , Naoaki Taoka , Yoshihiko Yasohara
发明人： Noriyuki Kizaki , Makoto Ueda , Daisuke Moriyama , Naoaki Taoka , Yoshihiko Yasohara
IPC分类号： C07H21/04 , C12N9/02 , C12P21/02 , C12P13/00 , C07C255/01
CPC分类号： C12N9/0006 , C12P7/04 , C12P7/62 , C12P13/002 , C12P41/002
摘要： The present invention is to provide a process for efficiently producing an optically active alcohol including (R)-3-hydroxy-3-phenylpropanenitrile. One of the features of the present invention is a polypeptide having an activity of asymmetrically reducing 3-oxo-3-phenylpropanenitrile isolated from a microorganism belonging to the genus Candida to produce (R)-3-hydroxy-3-phenylpropanenitrile, DNA encoding the polypeptide and a transformant of producing the polypeptide. Another feature of the present invention is a process for producing an optically active alcohol such as (R)-3-hydroxy-3-phenylpropanenitrile by reducing a carbonyl compound such as 3-oxo-3-phenylpropanenitrile by use of the polypeptide or the transformant.
摘要翻译：本发明提供一种有效制备包含（R）-3-羟基-3-苯基丙腈的光学活性醇的方法。本发明的特征之一是具有不对称还原从属于念珠菌属的微生物分离的3-氧代-3-苯基丙腈的活性的多肽，以产生（R）-3-羟基-3-苯基丙腈，编码多肽和产生多肽的转化体。本发明的另一个特征是通过使用多肽或转化体还原羰基化合物如3-氧代-3-苯基丙腈来制备光学活性醇如（R）-3-羟基-3-苯基丙腈的方法。

10. 发明授权

US07332312B2 Carbonyl reductase, gene thereof and use of the same 有权
标题翻译：羰基还原酶，其基因及其用途
公开(公告)号：US07332312B2
公开(公告)日：2008-02-19
申请号：US10512908
申请日：2003-04-30
申请人： Noriyuki Kizaki , Miho Horikawa , Yoshihiko Yasohara
发明人： Noriyuki Kizaki , Miho Horikawa , Yoshihiko Yasohara
IPC分类号： C12N1/20 , C12N9/02 , C12N1/21 , C12N15/00 , C07H21/04 , C12P7/22
CPC分类号： C12N9/0006 , C12Y101/01184
摘要： The present invention provides a novel polypeptide forming (R)-2-chloro-1-(3′-chlorophenyl)ethanol, a polynucleotide coding for said polypeptide, and use of the same.The present invention relates to a polypeptide having the following physical and chemical properties (1) to (4): (1) activity: acting on 2-chloro-1-(3′-chlorophenyl)ethanone with NADPH or NADH as a coenzyme, to form (R)-2-chloro-1-(31-chlorophenyl)ethanol; (2) optimum pH for activity: 5.0 to 6.0; (3) optimum temperature for activity: 40° C. to 50° C.; (4) molecular weight: about 40,000 as determined by gel filtration analysis, about 30,000 as determined by SDS polyacrylamide gel electrophoresis analysis. The present invention also relates to a polypeptide comprising the amino acid sequence shown under SEQ ID NO:1 in the sequence listing, a polynucleotide coding for said polypeptide, and a transformant producing said polypeptide at high levels.
摘要翻译：本发明提供形成（R）-2-氯-1-（3'-氯苯基）乙醇的新型多肽，编码所述多肽的多核苷酸及其用途。本发明涉及具有以下物理和化学性质（1）至（4）的多肽：（1）活性：以NADPH或NADH作为辅酶作用于2-氯-1-（3'-氯苯基）乙酮，形成（R）-2-氯-1-（31-氯苯基）乙醇; （2）活性最佳pH：5.0〜6.0; （3）最适温度为40℃〜50℃。（4）分子量：约40,000，通过凝胶过滤分析测定，约30,000，通过SDS聚丙烯酰胺凝胶电泳分析测定。本发明还涉及包含序列表中SEQ ID NO：1所示氨基酸序列的多肽，编码所述多肽的多核苷酸，以及以高水平产生所述多肽的转化体。

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