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公开(公告)号：US10961516B2
公开(公告)日：2021-03-30
申请号：US16344779
申请日：2016-11-04
申请人： ASYMCHEM LABORATORIES (TIANJIN) CO., LTD. , ASYMCHEM LIFE SCIENCE (TIANJIN) CO., LTD. , TIANJIN ASYMCHEM PHARMACEUTICALS CO., LTD. , ASYMCHEM LABORATORIES (FUXIN) CO., LTD. , JILIN ASYMCHEM LABORATORIES CO., LTD.
发明人： Hao Hong , Gage James , Jiangping Lu , Na Zhang , Wenyan Yu , Fang Liu , Yanjun Li , Xin Huang , Juan Gao , Kejian Zhang , Yulei Ma , Junlu Wei
摘要： Provided are a proline hydroxylase and uses thereof. The proline hydroxylase comprises (a) a protein having the amino acid sequence as shown in SEQ ID NO: 2; (b) a protein having an amino acid sequence of SEQ HD NO: 2 with a mutation of one or more amino acids and having a proline hydroxylase activity; or (c) a protein retaining the mutation of one or more amino acids as in (b), and having the proline hydroxylase activity and having at least 78% homology with the amino acid sequence of the protein in (b). Protein having the amino acid sequence as shown in SEQ HD NO: 2 and mutants obtained by genetically engineering have higher catalytic specificity or significantly increased catalytic activity when compared to proline hydroxylases in prior art.
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公开(公告)号：US11827909B2
公开(公告)日：2023-11-28
申请号：US17118169
申请日：2020-12-10
申请人： ASYMCHEM LABORATORIES (TIANJIN) CO., LTD. , ASYMCHEM LIFE SCIENCE (TIANJIN) CO., LTD. , TIANJIN ASYMCHEM PHARMACEUTICALS CO., LTD. , ASYMCHEM LABORATORIES (FUXIN) CO., LTD. , JILIN ASYMCHEM LABORATORIES CO., LTD.
发明人： Hao Hong , Gage James , Jiangping Lu , Na Zhang , Wenyan Yu , Fang Liu , Yanjun Li , Xin Huang , Juan Gao , Kejian Zhang , Yulei Ma , Junlu Wei
CPC分类号： C12N9/0071 , C12N15/70 , C12N15/81 , C12Y114/11002
摘要： Provided are a proline hydroxylase and uses thereof. The proline hydroxylase comprises having the amino acid sequence of SEQ ID NO: 2 with the exception of a mutation of one or more amino acids; wherein the mutation of one or more amino acids must comprises E27K, and the mutation of one or more amino acids selected from the group consisting of: H14R, L16N, T25R, F26L, E27K, D30S, S33N, E34N, E34G, E34L, E34S, E34D, Y35W, Y35K, S37W, S37F, S37E, S37N, S37T, S37C, W40F, K41E, D54G, H55Q, S57L, I58T, I58Y, I58A, I58R, I58V, I58S, I58C, K86P, T91A, F95Y, C97Y, I98V, K106V, K106T, K106Q, F111S, K112E, K112R, S154A, K162E, L166M, I118F, I118V, I118R, H119R, H119F, I120V, K123D, K123N, K123Q, K123S, K123I, K123T, T130N, D134G, V135K, N165H, D173G, K209R, I223V and S225A, and having proline hydroxylase activity.
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公开(公告)号：US20150119573A1
公开(公告)日：2015-04-30
申请号：US14394079
申请日：2012-12-27
申请人： ASYMCHEM LABORATORIES (TIANJIN)CO., LTD. , ASYMCHEM LIFE SCIENCE (TIANJIN) CO., LTD , TIANJIN ASYMCHEM PHARMACEUTICAL CO., LTD. , ASYMCHEM LABORATORIES (FUXIN) CO., LTD. , JILIN ASYMCHEM LABORATORIES CO. LTD.
发明人： Hao Hong , James Gage , Chaoyong Chen , Jiangping Lu , Yan Zhou , Shuangyong Liu
IPC分类号： C07D475/04 , C07D317/32 , C07D317/26 , C07C221/00 , C07D239/50 , C07C209/62 , C07D317/28 , C07D303/48 , C07C225/06
CPC分类号： C07D475/04 , C07C209/62 , C07C221/00 , C07C225/06 , C07D239/50 , C07D303/48 , C07D317/26 , C07D317/28 , C07D317/32
摘要： Disclosed is a method for synthesizing sapropterin dihydrochloride. The present disclosure reduces a synthesis route of the sapropterin dihydrochloride, and resolves a racemate intermediate or an intermediate having a low antimer isomerism value by using a chiral resolving reagent, thereby obtaining an intermediate having a high antimer isomerism value. Raw materials are cheap and readily available, and the cost is significantly reduced, hence providing an effective scheme for mass industrial production of the sapropterin dihydrochloride.
摘要翻译： 披露了一种合成沙rop in二盐酸盐的方法。 本公开内容减少了沙棘蛋白二盐酸盐的合成途径，并且通过使用手性拆分试剂拆分外消旋体中间体或具有低antimer异构值的中间体，从而获得具有高antimer异构值的中间体。 原材料便宜，易于获得，成本显着降低，为大规模工业生产四氢叶酸二盐酸盐提供了有效的方案。
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公开(公告)号：US20150105555A1
公开(公告)日：2015-04-16
申请号：US14391712
申请日：2012-12-27
申请人： ASYMCHEM LABORATORIES (TIANJIN) CO., LTD. , ASYMCHEM LIFE SCIENCE (TIANJIN) CO., LTD , TIANJIN ASYMCHEM PHARMACEUTICAL CO., LTD , ASYMCHEM LABORATORIES (FUXIN) CO., LTD. , JILIN ASYMCHEM LABORATORIES CO., LTD.
发明人： Hao Hong , James Gage , Chaoyong Chen , Jiangping Lu , Yan Zhou , Shuangyong Liu
IPC分类号： C07D475/04 , C07D317/32 , C07D317/26 , C07D301/12 , C07C221/00 , C07D239/50 , C07D301/14 , C07D301/03 , C07D317/28
CPC分类号： C07D475/04 , C07C221/00 , C07D239/50 , C07D301/03 , C07D301/12 , C07D301/14 , C07D317/26 , C07D317/28 , C07D317/32
摘要： Disclosed is a method for synthesizing sapropterin dihydrochloride. The present disclosure reduces a synthesis route of the sapropterin dihydrochloride, introduces a chiral center in an asymmetric synthesis manner, in which a tetrahydrofuran solution containing a samarium catalyst is adopted as a catalyst, and obtains a target compound having a high antimer isomerism value by means of selective catalysis. The yield is improved, raw materials are cheap and readily available, and the cost is significantly reduced, hence providing an effective scheme for mass industrial production of the sapropterin dihydrochloride.
摘要翻译： 披露了一种合成沙rop in二盐酸盐的方法。 本公开内容减少了沙棘蛋白二盐酸盐的合成途径，以不对称合成方式引入手性中心，其中采用含有钐催化剂的四氢呋喃溶液作为催化剂，并通过方法获得具有高抗反义异构性值的目标化合物 的选择性催化。 产量提高，原料便宜，易于获得，成本显着降低，为大规模工业生产四氢叶酸二盐酸盐提供了有效的方案。
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公开(公告)号：US09371326B2
公开(公告)日：2016-06-21
申请号：US14394079
申请日：2012-12-27
申请人： ASYMCHEM LABORATORIES (TIANJIN) CO., LTD , ASYMCHEM LIFE SCIENCE (TIANJIN) CO., LTD , TIANJIN ASYMCHEM PHARMACEUTICAL CO., LTD , ASYMCHEM LABORATORIES (FUXIN) CO., LTD , JILIN ASYMCHEM LABORATORIES CO.,LTD
发明人： Hao Hong , James Gage , Chaoyong Chen , Jiangping Lu , Yan Zhou , Shuangyong Liu
IPC分类号： C07D475/04 , C07D239/50 , C07D239/48 , C07D239/47 , C07D303/48 , C07D317/26 , C07D317/28 , C07D317/32 , C07C209/62 , C07C221/00 , C07C225/06
CPC分类号： C07D475/04 , C07C209/62 , C07C221/00 , C07C225/06 , C07D239/50 , C07D303/48 , C07D317/26 , C07D317/28 , C07D317/32
摘要： Disclosed is a method for synthesizing sapropterin dihydrochloride. The present disclosure reduces a synthesis route of the sapropterin dihydrochloride, and resolves a racemate intermediate or an intermediate having a low antimer isomerism value by using a chiral resolving reagent, thereby obtaining an intermediate having a high antimer isomerism value. Raw materials are cheap and readily available, and the cost is significantly reduced, hence providing an effective scheme for mass industrial production of the sapropterin dihydrochloride.
摘要翻译： 披露了一种合成沙rop in二盐酸盐的方法。 本公开内容减少了沙棘蛋白二盐酸盐的合成途径，并且通过使用手性拆分试剂拆分外消旋体中间体或具有低antimer异构值的中间体，从而获得具有高antimer异构值的中间体。 原材料便宜，易于获得，成本显着降低，为大规模工业生产四氢叶酸二盐酸盐提供了有效的方案。
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公开(公告)号：US09365573B2
公开(公告)日：2016-06-14
申请号：US14391712
申请日：2012-12-27
申请人： ASYMCHEM LABORATORIES (TIANJIN) CO., LTD , ASYMCHEM LIFE SCIENCE (TIANJIN) CO., LTD , TIANJIN ASYMCHEM PHARMACEUTICAL CO., LTD , ASYMCHEM LABORATORIES (FUXIN) CO., LTD , JILIN ASYMCHEM LABORATORIES CO., LTD
发明人： Hao Hong , James Gage , Chaoyong Chen , Jiangping Lu , Yan Zhou , Shuangyong Liu
IPC分类号： C07D475/04 , C07D239/50 , C07D239/48 , C07D239/47 , C07D303/48 , C07D317/26 , C07D317/28 , C07D317/32 , C07C209/62 , C07C221/00 , C07C225/06 , C07D301/03 , C07D301/12 , C07D301/14
CPC分类号： C07D475/04 , C07C221/00 , C07D239/50 , C07D301/03 , C07D301/12 , C07D301/14 , C07D317/26 , C07D317/28 , C07D317/32
摘要： Disclosed is a method for synthesizing sapropterin dihydrochloride. The present disclosure reduces a synthesis route of the sapropterin dihydrochloride, introduces a chiral center in an asymmetric synthesis manner, in which a tetrahydrofuran solution containing a samarium catalyst is adopted as a catalyst, and obtains a target compound having a high antimer isomerism value by means of selective catalysis. The yield is improved, raw materials are cheap and readily available, and the cost is significantly reduced, hence providing an effective scheme for mass industrial production of the sapropterin dihydrochloride.
摘要翻译： 披露了一种合成沙rop in二盐酸盐的方法。 本公开内容减少了沙棘蛋白二盐酸盐的合成途径，以不对称合成方式引入手性中心，其中采用含有钐催化剂的四氢呋喃溶液作为催化剂，并通过方法获得具有高抗反义异构性值的目标化合物 的选择性催化。 产量提高，原料便宜，易于获得，成本显着降低，为大规模工业生产四氢叶酸二盐酸盐提供了有效的方案。
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公开(公告)号：US11407982B2
公开(公告)日：2022-08-09
申请号：US16756649
申请日：2017-11-06
发明人： Hao Hong , Gage James , Jiangping Lu , Xuecheng Jiao , Na Zhang , Rui Li , Kejian Zhang
摘要： Disclosed are transaminase mutants and use thereof. The amino acid sequence of the transaminase mutant is obtained by the mutation of the amino acid sequence as shown in SEQ ID NO: 1, and the mutation at least comprises one of the following mutation sites: the 19-th site, the 41-th site, the 43-th site, the 72-th site, the 76-th site, the 92-th site, the 107-th site, the 125-th site, the 132-th site, the 226-th site, the 292-th site, the 295-th site, the 308-th site, and the 332-th site; and the 19-th site is mutated into a serine, the 41-th site is mutated into a serine, the 43-th site is mutated into an asparagine, a glycine in the 72-th site is mutated into a leucine, etc.; or the amino acid sequence of the transaminase mutant has the mutation sites in the mutanted amino acid sequence, and has more than 80% homology to the mutanted amino acid sequence.
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公开(公告)号：US11952575B2
公开(公告)日：2024-04-09
申请号：US16652291
申请日：2017-11-15
发明人： Hao Hong , Gage James , Jiangping Lu , Xingfu Xu , Wenyan Yu , Xin Huang , Yulei Ma , Yibing Cheng
CPC分类号： C12N15/70 , C12P13/001 , C12Y206/01
摘要： A transaminase mutant and use hereof, the amino acid sequence of the transaminase mutant is an amino acid sequence in which the amino acid sequence as represented by SEQ ID NO: 1 is mutated, the mutated amino acid position being one or more selected from among F89, K193, P243, V234, I262, Q280, V379, R416, A417 and C418. The enzymatic activity and/or stability of the transaminase mutant is improved.
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公开(公告)号：US20210292717A1
公开(公告)日：2021-09-23
申请号：US17266461
申请日：2018-08-17
发明人： Hao Hong , Gage James , Jiangping Lu , Na Zhang , Xuecheng Jiao , Rui Li , Kejian Zhang , Yu Zhang , Yiming Yang
摘要： Provided is an amino acid dehydrogenase mutant. The amino acid sequence of the mutant is obtained by mutating the amino acid sequence shown in SEQ ID NO:1. The mutation includes at least one of the following mutation sites: 64th, 94th, 133rd, 137th, 148th, 168th, 173rd, 183 rd, 191st, 207th, 229th, 248th, 255th and 282nd sites; or the amino acid sequence of the amino acid dehydrogenase mutant is an amino acid sequence having the mutation sites in the mutated amino acid sequence and having a 80% or more homology with the mutated amino acid sequence. The mutant enzyme activity is more than 50 times higher than that of wild amino acid dehydrogenase, and the enzyme specificity is also correspondingly improved.
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公开(公告)号：US11359219B2
公开(公告)日：2022-06-14
申请号：US16966528
申请日：2018-02-05
发明人： Hao Hong , Gage James , Jiangping Lu , Xingfu Xu , Yuxia Cui , Na Zhang , Xuewu Dong , Wenyan Yu , Xin Huang , Mingmin Hao , Yulei Ma , Yibing Cheng , Jiadong Zhao
摘要： The invention provides a transaminase mutant and application thereof, wherein the amino acid sequence of the transaminase mutant is formed after mutation of the amino acid sequence as shown in SEQ ID NO: 1, and mutated amino acid sites comprise T7C+S47C sites. The transaminase mutant having the mutation sites can be further prepared into an immobilized enzyme through an immobilization technology, the immobilized enzyme has relatively high activity and high stability, can be recycled for multiple times, and is applicable to continuous flow reaction in a packed bed.
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