公开(公告)号：US20060046289A1

公开(公告)日：2006-03-02

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： C12P7/22 ,  C07H21/04 ,  C12P21/06 ,  C12N9/02 ,  C12N1/21

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。

公开(公告)号：US5654472A

公开(公告)日：1997-08-05

申请号：US553558

申请日：1995-12-18

申请人： Yoshihiko Yasohara ,  Kenji Miyamoto ,  Noriyuki Kizaki ,  Shigeru Kawano ,  Junzo Hasegawa

发明人： Yoshihiko Yasohara ,  Kenji Miyamoto ,  Noriyuki Kizaki ,  Shigeru Kawano ,  Junzo Hasegawa

IPC分类号： C07C33/26 ,  C07C33/46 ,  C07C69/28 ,  C07C69/30 ,  C07C69/63 ,  C07C309/66 ,  C07C309/73 ,  C07D249/08 ,  C07D301/30 ,  C07D303/14 ,  C07D521/00 ,  C12P7/20 ,  C12P7/62 ,  C12P41/00 ,  C07C51/36 ,  C07C31/20 ,  C07C69/66

CPC分类号： C07D249/08 ,  C07C309/66 ,  C07C309/73 ,  C07C33/26 ,  C07C33/46 ,  C07C69/28 ,  C07C69/30 ,  C07C69/63 ,  C07D231/12 ,  C07D233/56 ,  C07D303/14 ,  C12P41/004 ,  C12P7/20 ,  C12P7/62

摘要： The present invention relates to a novel glycerol derivative and a process for preparing the same, and a process for preparing a triazole derivative.According to the present invention, an optical active 2-arylglycerol derivative which is a novel and useful as a synthetic intermediate of medicament can be provided and furthermore, (R)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazole-1-yl)-propane-1,2-diol which is useful as an antifungal agent can be prepared.

摘要翻译： PCT No.PCT / JP95 / 00749 Sec。 371 1995年12月18日第 102（e）1995年12月18日日期PCT提交1995年4月17日PCT公布。 出版物WO95 / 28374 日期：1995年10月26日本发明涉及新型甘油衍生物及其制备方法，以及制备三唑衍生物的方法。 根据本发明，可以提供新的可用作药物合成中间体的光学活性2-芳基甘油衍生物，此外，（R）-2-（2,4-二氟苯基）-3-（1H- 1,2,4-三唑-1-基） - 丙烷-1,2-二醇，可用作抗真菌剂。

公开(公告)号：US20090029430A1

公开(公告)日：2009-01-29

申请号：US11665065

申请日：2005-10-20

申请人： Noriyuki Kizaki ,  Mokoto Ueda ,  Daisuke Moriyama ,  Naoaki Taoka ,  Yoshihiko Yasohara

发明人： Noriyuki Kizaki ,  Mokoto Ueda ,  Daisuke Moriyama ,  Naoaki Taoka ,  Yoshihiko Yasohara

IPC分类号： C12P7/02 ,  C07H21/04 ,  C07K14/00 ,  C12N15/63 ,  C12N1/21

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 。

公开(公告)号：US20070178565A1

公开(公告)日：2007-08-02

申请号：US11730549

申请日：2007-04-02

申请人： Noriyuki Kizaki ,  Tozo Nishiyama ,  Yoshihiko Yasohara

发明人： Noriyuki Kizaki ,  Tozo Nishiyama ,  Yoshihiko Yasohara

IPC分类号： C12P17/04 ,  C07H21/04 ,  C12P21/06 ,  C12N9/06 ,  C12N1/21 ,  C12N15/74

CPC分类号： C12P17/10 ,  C12N9/0006 ,  C12P7/02 ,  C12P7/22

摘要： The present invention provides a novel polypeptide efficiently forming (R)-N-benzyl-3-pyrrolidinol, 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 N-benzyl-3-pyrrolidinone with NADH or NADPH as a coenzyme, to form (R)-N-benzyl-3-pyrrolidinol; (2) optimum pH for activity: 5.5 to 6.0; (3) optimum temperature for activity: 50° C. to 55° C.; (4) molecular weight: about 55,000 as determined by gel filtration analysis, about 28,000 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： 本发明提供了有效形成（R）-N-苄基-3-吡咯烷醇的新型多肽，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NADH或NADPH作为辅酶作用于N-苄基-3-吡咯烷酮，形成（R） - N-苄基-3-吡咯烷醇; （2）活性最佳pH：5.5〜6.0; （3）活性最佳温度：50〜55℃。 （4）通过凝胶过滤分析确定的分子量：约55,000，通过SDS聚丙烯酰胺凝胶电泳分析确定约28,000。 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。

公开(公告)号：US07220564B2

公开(公告)日：2007-05-22

申请号：US10528000

申请日：2003-09-19

申请人： Noriyuki Kizaki ,  Tozo Nishiyama ,  Yoshihiko Yasohara

发明人： Noriyuki Kizaki ,  Tozo Nishiyama ,  Yoshihiko Yasohara

IPC分类号： C12N9/02 ,  C12N9/52 ,  C12N1/20 ,  C12P7/22 ,  C12P21/06 ,  C07H21/02

CPC分类号： C12P17/10 ,  C12N9/0006 ,  C12P7/02 ,  C12P7/22

摘要： The present invention provides a novel polypeptide efficiently forming (R)-N-benzyl-3-pyrrolidinol, 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 N-benzyl-3-pyrrolidinone with NADH or NADPH as a coenzyme, to form (R)-N-benzyl-3-pyrrolidinol; (2) optimum pH for activity: 5.5 to 6.0; (3) optimum temperature for activity: 50° C. to 55° C.; (4) molecular weight: about 55,000 as determined by gel filtration analysis, about 28,000 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： 本发明提供了有效形成（R）-N-苄基-3-吡咯烷醇的新型多肽，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NADH或NADPH作为辅酶作用于N-苄基-3-吡咯烷酮，形成（R） - N-苄基-3-吡咯烷醇; （2）活性最佳pH：5.5〜6.0; （3）活性最佳温度：50〜55℃。 （4）通过凝胶过滤分析确定的分子量：约55,000，通过SDS聚丙烯酰胺凝胶电泳分析确定约28,000。 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。

公开(公告)号：US06472544B1

公开(公告)日：2002-10-29

申请号：US09509998

申请日：2000-08-16

申请人： Noriyuki Kizaki ,  Yukio Yamada ,  Yoshihiko Yasohara ,  Akira Nishiyama ,  Makoto Miyazaki ,  Masaru Mitsuda ,  Takeshi Kondo ,  Noboru Ueyama ,  Kenji Inoue

发明人： Noriyuki Kizaki ,  Yukio Yamada ,  Yoshihiko Yasohara ,  Akira Nishiyama ,  Makoto Miyazaki ,  Masaru Mitsuda ,  Takeshi Kondo ,  Noboru Ueyama ,  Kenji Inoue

IPC分类号： C07D31906

CPC分类号： C07D319/06 ,  C07B2200/07 ,  C07C67/343 ,  C07C253/30 ,  C12P7/62 ,  C07C69/716 ,  C07C255/21

摘要： This invention provides a process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives, which are of value as intermediates of drugs, from inexpensive starting materials without using any special equipment such as that required for super-low temperature reactions. A process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives which comprises reacting an acetic acid derivative at a temperature of not less than −30° C. with an enolate prepared by permitting either a base or a metal having a valency of 0 to act on the derivative to produce a hydroxyoxohexanoic acid derivative, reducing this compound with the aid of a strain of microorganism to provide a halomethyldioxanylacetic acid derivative, treating this compound with an acetalizing agent in the presence of an acid catalyst to provide a halomethyldioxanylacetic acid derivative, reacted with an acyloxylating agent to provide a acyloxymethyldioxanylacetic acid derivative, and subjecting this compound to solvolysis in the presence of a base.

摘要翻译： 本发明提供了从廉价起始原料生产具有价值作为药物中间体的光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物的方法，而不使用任何特殊设备 例如超低温反应所需的方法。一种制备光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物的方法，其包括在不是的温度下使乙酸衍生物反应 小于-30℃，通过使碱金属或化合价为0的金属作用于衍生物以制备羟基氧代己酸衍生物而制备的烯醇化物，借助于微生物菌株还原该化合物以提供 卤甲基二恶烷基乙酸衍生物，在酸催化剂存在下用缩醛化剂处理该化合物，得到卤代甲基二恶烷基乙酸衍生物，与酰氧基化剂反应，得到酰氧基甲基二恶烷基乙酸 在碱的存在下，将该化合物施用于溶剂分解。

公开(公告)号：US20110236955A1

公开(公告)日：2011-09-29

申请号：US11576560

申请日：2005-09-26

申请人： Noriyuki Kizaki ,  Noriyuki Ito ,  Yoshihiko Yasohara ,  Toru Nagasawa

发明人： Noriyuki Kizaki ,  Noriyuki Ito ,  Yoshihiko Yasohara ,  Toru Nagasawa

IPC分类号： C12N9/80 ,  C12N15/55 ,  C12N15/63 ,  C12N1/21

CPC分类号： C12N9/80

摘要： The present invention provides an efficient method of producing an arylacylamidase. In an aspect, the present invention provides (a) a DNA comprising the base sequence shown in the sequence listing under SEQ ID NO:1, or (b) a DNA capable of hybridizing, under stringent conditions, with a DNA comprising the base sequence complementary to the base sequence shown in the sequence listing under SEQ ID NO:1 and coding for a polypeptide having arylacylamidase activity. In another aspect, the invention provides a polypeptide encoded by the DNA mentioned above and having arylacylamidase activity, a vector containing the DNA mentioned above, a transformant which is transformed using the DNA or the vector mentioned above, and a method for producing an arylacylamidase which comprises cultivating the transformant mentioned above and obtaining the arylacylamidase from the culture medium.

摘要翻译： 本发明提供了生产芳基酰胺酶的有效方法。 一方面，本发明提供（a）包含SEQ ID NO：1中的序列表中所示的碱基序列的DNA，或（b）能够在严格条件下与包含碱基序列的DNA杂交的DNA 与SEQ ID NO：1中的序列表中所示的碱基序列互补，并编码具有芳基酰胺酶活性的多肽。 另一方面，本发明提供由上述DNA编码并具有芳基酰胺酶活性的多肽，含有上述DNA的载体，使用上述DNA或载体转化的转化体及其制备方法， 包括培养上述转化体并从培养基中获得芳酰胺酰胺酶。

公开(公告)号：US6046354A

公开(公告)日：2000-04-04

申请号：US143653

申请日：1998-08-31

申请人： Yoshihiko Yasohara ,  Kenji Miyamoto ,  Noriyuki Kizaki ,  Shigeru Kawano ,  Junzo Hasegawa

发明人： Yoshihiko Yasohara ,  Kenji Miyamoto ,  Noriyuki Kizaki ,  Shigeru Kawano ,  Junzo Hasegawa

IPC分类号： C07C33/26 ,  C07C33/46 ,  C07C69/28 ,  C07C69/30 ,  C07C69/63 ,  C07C309/66 ,  C07C309/73 ,  C07D249/08 ,  C07D301/30 ,  C07D303/14 ,  C07D521/00 ,  C12P7/20 ,  C12P7/62 ,  C12P41/00 ,  C07C69/66 ,  C07C69/67

CPC分类号： C07D249/08 ,  C07C309/66 ,  C07C309/73 ,  C07C33/26 ,  C07C33/46 ,  C07C69/28 ,  C07C69/30 ,  C07C69/63 ,  C07D231/12 ,  C07D233/56 ,  C07D303/14 ,  C12P41/004 ,  C12P7/20 ,  C12P7/62

摘要： A novel glycerol derivative, a process for preparing the same, and a process for preparing a triazole derivative. An optically active 2-arylglycerol derivative which is novel and useful as a synthetic intermediate of medicament is provided, and furthermore, (R)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazole-1-yl)-propane-1,2-diol, which is useful as an antifungal agent, is prepared.

摘要翻译： 一种新型甘油衍生物，其制备方法和制备三唑衍生物的方法。 提供新的可用作药物合成中间体的光学活性2-芳基甘油衍生物，此外，（R）-2-（2,4-二氟苯基）-3-（1H-1,2,4-三唑 -1-基） - 丙烷-1,2-二醇，其可用作抗真菌剂。

公开(公告)号：US06903225B2

公开(公告)日：2005-06-07

申请号：US10242453

申请日：2002-09-13

申请人： Noriyuki Kizaki ,  Yukio Yamada ,  Yoshihiko Yasohara ,  Akira Nishiyama ,  Makoto Miyazaki ,  Masaru Mitsuda ,  Takeshi Kondo ,  Noboru Ueyama ,  Kenji Inoue

发明人： Noriyuki Kizaki ,  Yukio Yamada ,  Yoshihiko Yasohara ,  Akira Nishiyama ,  Makoto Miyazaki ,  Masaru Mitsuda ,  Takeshi Kondo ,  Noboru Ueyama ,  Kenji Inoue

IPC分类号： C07C67/343 ,  C07C253/30 ,  C07C255/21 ,  C07D319/06 ,  C12P7/62 ,  C12P1/04 ,  C12P17/06

CPC分类号： C07D319/06 ,  C07B2200/07 ,  C07C67/343 ,  C07C253/30 ,  C12P7/62 ,  C07C69/716 ,  C07C255/21

摘要： This invention provides a process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives, which are of value as intermediates of drugs, from inexpensive starting materials without using any special equipment such as that required for super-low temperature reactions.A process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives which comprises reacting an acetic acid derivative at a temperature of not less than −30° C. with an enolate prepared by permitting either a base or a metal having a valency of 0 to act on the derivative to produce a hydroxyoxohexanoic acid derivative, reducing this compound with the aid of a strain of microorganism to provide a halomethyldioxanylacetic acid derivative, treating this compound with an acetalizing agent in the presence of an acid catalyst to provide a halomethyl-dioxanylacetic acid derivative, reacted with an acyloxylating agent to provide a acyloxymethyldioxanylacetic acid derivative, and subjecting this compound to solvolysis in the presence of a base.

摘要翻译： 本发明提供了从廉价起始原料生产具有价值作为药物中间体的光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物的方法，而不使用任何特殊设备 例如超低温反应所需的。 一种制备光学活性的2- [6-（羟基甲基）-1,3-二恶烷-4-基]乙酸衍生物的方法，其包括使不饱和-30℃的乙酸衍生物与烯醇化物 通过使碱金属或0价金属作用于衍生物以制备羟基己酸衍生物而制备，借助于微生物菌株还原该化合物以提供卤代甲基二恶烷基乙酸衍生物，用缩醛化处理该化合物 在酸催化剂存在下，提供卤代甲基 - 二恶烷基乙酸衍生物，与酰氧基化剂反应，得到酰氧基甲基二恶烷基乙酸衍生物，并在碱的存在下使其溶解。

公开(公告)号：US07531329B2

公开(公告)日：2009-05-12

申请号：US11730549

申请日：2007-04-02

申请人： Noriyuki Kizaki ,  Tozo Nishiyama ,  Yoshihiko Yasohara

发明人： Noriyuki Kizaki ,  Tozo Nishiyama ,  Yoshihiko Yasohara

IPC分类号： C12P17/04 ,  C07H21/04 ,  C12N1/20

CPC分类号： C12P17/10 ,  C12N9/0006 ,  C12P7/02 ,  C12P7/22

摘要： The present invention provides a novel polypeptide efficiently forming (R)-N-benzyl-3-pyrrolidinol, a polynucleotide coding for said polypeptide, and use of the same. The present invention relates to a polypeptide having the physical and chemical properties (1) to (4): (1) activity acting on N-benzyl-3-pyrrolidinone with NADH or NADPH as a coenzyme, to form (R)-N-benzyl-3-pyrrolidinol; (2) optimum pH of 5.5 to 6.0 for activity ; (3) optimum temperature of 50° C. to 55° C. for activity ; (4) molecular weight of about 55,000 as determined by gel filtration analysis, and about 28,000 as determined by SDS polyacrylamide gel electrophoresis analysis. The present invention also relates to a polypeptide comprising the amino acid sequence of SEQ ID NO:1, a polynucleotide coding for said polypeptide, and a transformant producing said polypeptide at high levels.

摘要翻译： 本发明提供了有效形成（R）-N-苄基-3-吡咯烷醇的新型多肽，编码所述多肽的多核苷酸及其用途。 本发明涉及具有物理和化学性质（1）至（4）的多肽：（1）以NADH或NADPH作为辅酶作用于N-苄基-3-吡咯烷酮的活性以形成（R）-N- 苄基-3-吡咯烷醇; （2）活性最佳pH为5.5〜6.0; （3）活性最佳温度为50〜55℃; （4）通过凝胶过滤分析测定的约55,000的分子量，通过SDS聚丙烯酰胺凝胶电泳分析测定的约28,000。 本发明还涉及包含SEQ ID NO：1的氨基酸序列，编码所述多肽的多核苷酸和以高水平产生所述多肽的转化体的多肽。