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公开(公告)号：US11866749B2
公开(公告)日：2024-01-09
申请号：US17079010
申请日：2020-10-23
发明人： Hao Luo , Jochen Förster
IPC分类号： C12N9/88 , C12N9/78 , C12N9/02 , C12P17/10 , C12P13/22 , C12P7/22 , C12N1/16 , C12N1/14 , C12N1/20
CPC分类号： C12N9/78 , C12N1/14 , C12N1/16 , C12N1/20 , C12N9/0071 , C12N9/88 , C12P7/22 , C12P13/225 , C12P13/227 , C12P17/10 , C12Y114/16001 , C12Y114/16002 , C12Y114/16004 , C12Y305/04016 , C12Y402/01096
摘要： Described herein are recombinant microbial host cells comprising biosynthetic pathways and their use in producing oxidation products and downstream products, e.g., melatonin and related compounds, as well as enzyme variants, nucleic acids, vectors and methods useful for preparing and using such cells. In specific aspects, the present invention relates to monooxygenases, e.g., amino acid hydroxylases, with a modified cofactor-dependency, and to enzyme variants and microbial cells providing for an improved supply of cofactors.
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公开(公告)号：US20230263864A1
公开(公告)日：2023-08-24
申请号：US18015938
申请日：2021-07-15
CPC分类号： A61K38/44 , C12Y114/16002 , C12Y401/01028 , C12Y305/04016 , C12Y402/01096 , C12N15/52
摘要： The invention relates to microbial cells and microbial cells for use as a medicament, the cells expressing a recombinant nucleic acid encoding a eukaryotic tyrosine hydroxylase. The cells produce L-DOPA and dopamine.
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公开(公告)号：US10023889B2
公开(公告)日：2018-07-17
申请号：US15310040
申请日：2015-05-14
发明人： Yajun Yan , Yuheng Lin
CPC分类号： C12P13/227 , A23K20/10 , A23L2/52 , C12N9/0028 , C12N9/0071 , C12N9/88 , C12Y105/01034 , C12Y114/16001 , C12Y402/01096
摘要： 5-hydroxytryptophan (5-HTP), a precursor of serotonin, is produced in a microbial host cell. A modified bacterial phenylalanine 4-hydroxylase (P4H) catalyzes the tryptophan 5-hydroxylation reaction. Optionally the host cell includes a cofactor regeneration mechanism, allowing continuous production of 5-HTP without supplementation of exogenous cofactors.
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4.发明申请公开(公告)号：US20160230200A1
公开(公告)日：2016-08-11
申请号：US14916205
申请日：2014-09-05
发明人： JIANGFENG ZHU , NIELS BJERG JENSEN , XIAO CHEN , JOCHEN FÖRSTER , IRINA BORODINA
CPC分类号： C12P17/10 , C12N9/0006 , C12N9/0028 , C12N9/0071 , C12N9/1007 , C12N9/1022 , C12N9/1029 , C12N9/1085 , C12N9/1096 , C12N9/1205 , C12N9/1294 , C12N9/78 , C12N9/88 , C12N15/52 , C12P13/227 , C12Y101/01153 , C12Y105/01034 , C12Y114/16004 , C12Y201/01004 , C12Y202/01001 , C12Y203/01005 , C12Y203/01087 , C12Y205/01054 , C12Y206/01057 , C12Y207/01001 , C12Y207/09002 , C12Y305/04016 , C12Y401/01028 , C12Y402/01096 , C12Y402/03012
摘要： Recombinant microbial cells and methods for producing 5HTP, melatonin and related compounds using such cells are described. More specifically, the recombinant microbial cell may comprise exogenous genes encoding one or more of an L-tryptophan hydroxylase, a 5-hydroxy-L-tryptophan decarboxylyase, a serotonin acetyltransferase, an acetylserotonin O-methyltransferase; and means for providing tetrahydrobiopterin (THB), and can be further genetically modified to enrich one or more of tryptophan, S-adenosyl-L-methinonine and acetyl coenzyme A. Related sequences and vectors for use in preparing such recombinant microbial cells are also described.
摘要翻译： 描述了重组微生物细胞和使用这种细胞产生5HTP，褪黑激素和相关化合物的方法。 更具体地说，重组微生物细胞可以包含编码L-色氨酸羟化酶，5-羟基-L-色氨酸脱羧基酶，5-羟色胺乙酰转移酶，乙酰肌氨酸O-甲基转移酶中的一种或多种的外源基因; 和用于提供四氢生物蝶呤（THB）的方法，并且可以进一步进行基因修饰以富集一个或多个色氨酸，S-腺苷-L-亚甲基内酯和乙酰辅酶A.还描述了用于制备这种重组微生物细胞的相关序列和载体 。
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公开(公告)号：US20150037849A1
公开(公告)日：2015-02-05
申请号：US14382152
申请日：2013-02-28
发明人： Eric Michael Knight , Jiangfeng Zhu , Jochen Förster , Hao Luo
CPC分类号： C12P13/227 , C12N9/0004 , C12N9/0006 , C12N9/0028 , C12N9/0071 , C12N9/78 , C12N9/88 , C12N15/70 , C12N15/81 , C12P17/182 , C12Y101/01153 , C12Y105/01034 , C12Y114/16004 , C12Y305/04016 , C12Y402/01096 , C12Y402/03012
摘要： Recombinant microbial cells and methods for producing 5-hydroxytryptophan (5HTP) using such cells are described. More specifically, the recombinant microbial cell comprises an exogenous gene encoding an L-tryptophan hydroxylase, and means for providing tetrahydrobiopterin (THB). Related sequences and vectors for use in preparing such recombinant microbial cells are also described.
摘要翻译： 描述了使用这种细胞的重组微生物细胞和用于产生5-羟色氨酸（5HTP）的方法。 更具体地，重组微生物细胞包含编码L-色氨酸羟化酶的外源基因和提供四氢生物蝶呤（THB）的方法。 还描述了用于制备这种重组微生物细胞的相关序列和载体。
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公开(公告)号：US20180282774A1
公开(公告)日：2018-10-04
申请号：US16008566
申请日：2018-06-14
发明人： Yajun Yan , Yuheng Lin
CPC分类号： C12P13/227 , A23K20/10 , A23L2/52 , C12N9/0028 , C12N9/0071 , C12N9/88 , C12Y105/01034 , C12Y114/16001 , C12Y402/01096
摘要： 5-hydroxytryptophan (5-HTP), a precursor of serotonin, is produced in a microbial host cell. A modified bacterial phenylalanine 4-hydroxylase (P4H) catalyzes the tryptophan 5-hydroxylation reaction. Optionally the host cell includes a cofactor regeneration mechanism, allowing continuous production of 5-HTP without supplementation of exogenous cofactors.
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公开(公告)号：US20170362617A1
公开(公告)日：2017-12-21
申请号：US15541114
申请日：2015-12-31
CPC分类号： C12P17/182 , C12N9/0006 , C12N9/0036 , C12N9/78 , C12N9/88 , C12N15/52 , C12P7/00 , C12P7/22 , C12P13/001 , C12P13/225 , C12P13/227 , C12P17/10 , C12P17/12 , C12P17/16 , C12P17/18 , C12P19/60 , C12Y101/01153 , C12Y106/99 , C12Y305/04016 , C12Y401/01028 , C12Y402/01096 , C12Y402/03012
摘要： Provided herein are biocatalysts and systems thereof for pterin-dependent enzymes and pathways and methods of making and using the same. Provided herein in some embodiments are biocatalysts having a pterin source and a pterin-dependent enzymatic pathway biologically coupled to the pterin source. Tetrahydrobiopterin (referred to herein as BH4 or BH 4) can be the pterin source. The BH4 can be synthesized by a tetrahydrobiopterin synthesis pathway. The tetrahydrobiopterin synthesis pathway can include a GTP cyclohydrase; a pyruvoyl tetrahydropterin synthase; a sepiapterin reductase, and/or any combination thereof. The biocatalyst can further contain a pterin-dependent enzymatic pathway. The pterin-dependent enzymatic pathway can be amino acid mono-oxygenase, phenylalanine hydroxylase, tryptophan hydroxylase, tyrosine hydroxylase, nitric oxide synthase, alkylglycerol monooxygenase, and/or any combination thereof.
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公开(公告)号：US20170240939A1
公开(公告)日：2017-08-24
申请号：US15310040
申请日：2015-05-14
发明人： Yajun Yan , Yuheng Lin
CPC分类号： C12P13/227 , A23K20/10 , A23L2/52 , C12N9/0028 , C12N9/0071 , C12N9/88 , C12Y105/01034 , C12Y114/16001 , C12Y402/01096
摘要： 5-hydroxytryptophan (5-HTP), a precursor of serotonin, is produced in a microbial host cell. A modified bacterial phenylalanine 4-hydroxylase (P4H) catalyzes the tryptophan 5-hydroxylation reaction. Optionally the host cell includes a cofactor regeneration mechanism, allowing continuous production of 5-HTP without supplementation of exogenous cofactors.
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公开(公告)号：US20150024440A1
公开(公告)日：2015-01-22
申请号：US14382164
申请日：2013-02-28
发明人： Eric Michael Knight , Jiangfeng Zhu , Jochen Förster , Hao Luo
CPC分类号： C12P17/10 , C12N9/0006 , C12N9/0028 , C12N9/0071 , C12N9/1007 , C12N9/1029 , C12N9/78 , C12N9/88 , C12N15/70 , C12P13/227 , C12P17/182 , C12Y101/01153 , C12Y105/01034 , C12Y114/16004 , C12Y201/01004 , C12Y203/01087 , C12Y305/04016 , C12Y401/01028 , C12Y402/01096 , C12Y402/03012
摘要： Recombinant microbial cells and methods for producing melatonin and related compounds using such cells are described. More specifically, the recombinant microbial cell may comprise exogenous genes encoding one or more of an L-tryptophan hydroxylase, a 5-hydroxy-L-tryptophan decarboxylyase, a serotonin acetyltransferase, an acetylserotonin O-methyltransferase; an L-tryptophan decarboxy-lyase, and a tryptamine-5-hydroxylase, and means for providing tetrahydrobiopterin (THB). Related sequences and vectors for use in preparing such recombinant microbial cells are also described.
摘要翻译： 描述了重组微生物细胞和使用这种细胞产生褪黑激素和相关化合物的方法。 更具体地说，重组微生物细胞可以包含编码L-色氨酸羟化酶，5-羟基-L-色氨酸脱羧基酶，5-羟色胺乙酰转移酶，乙酰肌氨酸O-甲基转移酶中的一种或多种的外源基因; L-色氨酸脱羧裂解酶和色胺-5-羟化酶，以及提供四氢生物蝶呤（THB）的方法。 还描述了用于制备这种重组微生物细胞的相关序列和载体。
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