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1. 发明授权

US07667017B2 Isolated mevalonate pathway enzyme nucleic acids 有权
标题翻译：孤立的甲羟戊酸途径酶核酸
公开(公告)号：US07667017B2
公开(公告)日：2010-02-23
申请号：US11469587
申请日：2006-09-01
申请人： Jay D. Keasling , Vincent J. J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack D. Newman , Artem Valentinovich Khlebnikov
发明人： Jay D. Keasling , Vincent J. J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack D. Newman , Artem Valentinovich Khlebnikov
IPC分类号： C07H21/04 , C12P1/00 , C12P7/00 , C12N9/00 , C12N9/12 , C12N9/88 , C12N1/20 , C12N15/00
CPC分类号： C12N15/52 , C12N9/1205 , C12N9/88 , C12P9/00
摘要： Methods for synthesizing isopentenyl pyrophosphate are provided. A first method comprises introducing into a host microorganism a plurality of heterologous nucleic acid sequences, each coding for a different enzyme in the mevalonate pathway for producing isopentenyl pyrophosphate. A related method comprises introducing into a host microorganism an intermediate in the mevalonate pathway and at least one heterologous nucleic acid sequence, each sequence coding for an enzyme in the mevalonate pathway necessary for converting the intermediate into isopentenyl pyrophosphate. The invention also provides nucleic acid sequences, enzymes, expression vectors, and transformed host cells for carrying out the methods.
摘要翻译：提供了合成焦磷酸异戊烯酯的方法。第一种方法包括向宿主微生物中引入多个异源核酸序列，每个异源核酸序列编码甲羟戊酸途径中用于产生异戊烯基焦磷酸盐的不同酶。相关方法包括向宿主微生物中引入甲羟戊酸途径中的中间体和至少一个异源核酸序列，每个序列编码甲羟戊酸途径中的酶将中间体转化为异戊烯基焦磷酸。本发明还提供了用于实施该方法的核酸序列，酶，表达载体和转化的宿主细胞。

2. 发明授权

US07915026B2 Host cells for production of isoprenoid compounds 有权
标题翻译：用于生产类异戊二烯化合物的宿主细胞
公开(公告)号：US07915026B2
公开(公告)日：2011-03-29
申请号：US12576068
申请日：2009-10-08
申请人： Jay D. Keasling , Vincent J. J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack Newman , Artem Valentinovich Khlebnikov
发明人： Jay D. Keasling , Vincent J. J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack Newman , Artem Valentinovich Khlebnikov
IPC分类号： C12P1/00 , C12P7/00 , C12N9/00 , C12N9/02 , C12N9/12 , C12N9/88 , C12N1/20 , C12N15/00
CPC分类号： C12N15/52 , C12N9/1205 , C12N9/88 , C12P9/00
摘要： Methods for synthesizing isopentenyl pyrophosphate are provided. A first method comprises introducing into a host microorganism a plurality of heterologous nucleic acid sequences, each coding for a different enzyme in the mevalonate pathway for producing isopentenyl pyrophosphate. A related method comprises introducing into a host microorganism an intermediate in the mevalonate pathway and at least one heterologous nucleic acid sequence, each sequence coding for an enzyme in the mevalonate pathway necessary for converting the intermediate into isopentenyl pyrophosphate. The invention also provides nucleic acid sequences, enzymes, expression vectors, and transformed host cells for carrying out the methods.
摘要翻译：提供了合成焦磷酸异戊烯酯的方法。第一种方法包括向宿主微生物中引入多个异源核酸序列，每个异源核酸序列编码甲羟戊酸途径中用于产生异戊烯基焦磷酸盐的不同酶。相关方法包括向宿主微生物中引入甲羟戊酸途径中的中间体和至少一个异源核酸序列，每个序列编码甲羟戊酸途径中的酶将中间体转化为异戊烯基焦磷酸。本发明还提供了用于实施该方法的核酸序列，酶，表达载体和转化的宿主细胞。

3. 发明授权

US07736882B2 Host cells for production of isoprenoid compounds 有权
标题翻译：用于生产类异戊二烯化合物的宿主细胞
公开(公告)号：US07736882B2
公开(公告)日：2010-06-15
申请号：US11610686
申请日：2006-12-14
申请人： Jay D. Keasling , Vincent J. J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack Newman , Artem Valentinovich Khlebnikov
发明人： Jay D. Keasling , Vincent J. J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack Newman , Artem Valentinovich Khlebnikov
IPC分类号： C12P1/00 , C12P7/00 , C12N9/00 , C12N9/02 , C12N9/12 , C12N9/88 , C12N15/00 , C07H21/04
CPC分类号： C12N15/52 , C12N9/1205 , C12N9/88 , C12P9/00
摘要： Methods for synthesizing isopentenyl pyrophosphate are provided. A first method comprises introducing into a host microorganism a plurality of heterologous nucleic acid sequences, each coding for a different enzyme in the mevalonate pathway for producing isopentenyl pyrophosphate. A related method comprises introducing into a host microorganism an intermediate in the mevalonate pathway and at least one heterologous nucleic acid sequence, each sequence coding for an enzyme in the mevalonate pathway necessary for converting the intermediate into isopentenyl pyrophosphate. The invention also provides nucleic acid sequences, enzymes, expression vectors, and transformed host cells for carrying out the methods.
摘要翻译：提供了合成焦磷酸异戊烯酯的方法。第一种方法包括向宿主微生物中引入多个异源核酸序列，每个异源核酸序列编码甲羟戊酸途径中用于产生异戊烯基焦磷酸盐的不同酶。相关方法包括向宿主微生物中引入甲羟戊酸途径中的中间体和至少一个异源核酸序列，每个序列编码甲羟戊酸途径中的酶将中间体转化为异戊烯基焦磷酸。本发明还提供了用于实施该方法的核酸序列，酶，表达载体和转化的宿主细胞。

4. 发明授权

US07622282B2 Biosynthesis of isopentenyl pyrophosphate 有权
标题翻译：异戊烯焦磷酸的生物合成
公开(公告)号：US07622282B2
公开(公告)日：2009-11-24
申请号：US11610337
申请日：2006-12-13
申请人： Jay D. Keasling , Vincent J. J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack Newman , Artem Valentinovich Khlebnikov
发明人： Jay D. Keasling , Vincent J. J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack Newman , Artem Valentinovich Khlebnikov
IPC分类号： C12P1/00 , C12P7/00 , C12N9/00 , C12N9/02 , C12N9/12 , C12N9/88 , C12N1/20 , C12N15/00 , C07H21/04
CPC分类号： C12N15/52 , C12N9/1205 , C12N9/88 , C12P9/00
摘要： Methods for synthesizing isopentenyl pyrophosphate are provided. A first method comprises introducing into a host microorganism a plurality of heterologous nucleic acid sequences, each coding for a different enzyme in the mevalonate pathway for producing isopentenyl pyrophosphate. A related method comprises introducing into a host microorganism an intermediate in the mevalonate pathway and at least one heterologous nucleic acid sequence, each sequence coding for an enzyme in the mevalonate pathway necessary for converting the intermediate into isopentenyl pyrophosphate. The invention also provides nucleic acid sequences, enzymes, expression vectors, and transformed host cells for carrying out the methods.
摘要翻译：提供了合成焦磷酸异戊烯酯的方法。第一种方法包括向宿主微生物中引入多个异源核酸序列，每个异源核酸序列编码甲羟戊酸途径中用于产生异戊烯基焦磷酸盐的不同酶。相关方法包括向宿主微生物中引入甲羟戊酸途径中的中间体和至少一个异源核酸序列，每个序列编码甲羟戊酸途径中的酶将中间体转化为异戊烯基焦磷酸。本发明还提供了用于实施该方法的核酸序列，酶，表达载体和转化的宿主细胞。

5. 发明授权

US08288147B2 Host cells for production of isoprenoid compounds 有权
标题翻译：用于生产类异戊二烯化合物的宿主细胞
公开(公告)号：US08288147B2
公开(公告)日：2012-10-16
申请号：US13027517
申请日：2011-02-15
申请人： Jay D. Keasling , Vincent J.J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack Newman , Artem Valentinovich Khlebnikov
发明人： Jay D. Keasling , Vincent J.J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack Newman , Artem Valentinovich Khlebnikov
IPC分类号： C12P1/00 , C12P7/00 , C12N9/00 , C12N9/02 , C12N9/12 , C12N9/88 , C12N1/20 , C12N15/00 , C07H21/04
CPC分类号： C12N15/52 , C12N9/1205 , C12N9/88 , C12P9/00
摘要： Methods for synthesizing isopentenyl pyrophosphate are provided. A first method comprises introducing into a host microorganism a plurality of heterologous nucleic acid sequences, each coding for a different enzyme in the mevalonate pathway for producing isopentenyl pyrophosphate. A related method comprises introducing into a host microorganism an intermediate in the mevalonate pathway and at least one heterologous nucleic acid sequence, each sequence coding for an enzyme in the mevalonate pathway necessary for converting the intermediate into isopentenyl pyrophosphate. The invention also provides nucleic acid sequences, enzymes, expression vectors, and transformed host cells for carrying out the methods.
摘要翻译：提供了合成焦磷酸异戊烯酯的方法。第一种方法包括向宿主微生物中引入多个异源核酸序列，每个异源核酸序列编码甲羟戊酸途径中用于产生异戊烯基焦磷酸盐的不同酶。相关方法包括向宿主微生物中引入甲羟戊酸途径中的中间体和至少一个异源核酸序列，每个序列编码甲羟戊酸途径中的酶将中间体转化为异戊烯基焦磷酸。本发明还提供了用于实施该方法的核酸序列，酶，表达载体和转化的宿主细胞。

6. 发明授权

US07622283B2 Methods for synthesizing mevalonate 有权
标题翻译：合成甲羟戊酸的方法
公开(公告)号：US07622283B2
公开(公告)日：2009-11-24
申请号：US11610690
申请日：2006-12-14
申请人： Jay D. Keasling , Vinent J. J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack Newman , Artem Valentinovich Khlebnikov
发明人： Jay D. Keasling , Vinent J. J. Martin , Douglas J. Pitera , Seon-Won Kim , Sydnor T. Withers, III , Yasuo Yoshikuni , Jack Newman , Artem Valentinovich Khlebnikov
IPC分类号： C12P1/00 , C12P7/00 , C12N9/00 , C12N9/02 , C12N9/12 , C12N9/88 , C12N1/20 , C12N15/00 , C07H21/04
CPC分类号： C12N15/52 , C12N9/1205 , C12N9/88 , C12P9/00
摘要： Methods for synthesizing isopentenyl pyrophosphate are provided. A first method comprises introducing into a host microorganism a plurality of heterologous nucleic acid sequences, each coding for a different enzyme in the mevalonate pathway for producing isopentenyl pyrophosphate. A related method comprises introducing into a host microorganism an intermediate in the mevalonate pathway and at least one heterologous nucleic acid sequence, each sequence coding for an enzyme in the mevalonate pathway necessary for converting the intermediate into isopentenyl pyrophosphate. The invention also provides nucleic acid sequences, enzymes, expression vectors, and transformed host cells for carrying out the methods.
摘要翻译：提供了合成焦磷酸异戊烯酯的方法。第一种方法包括向宿主微生物中引入多个异源核酸序列，每个异源核酸序列编码甲羟戊酸途径中用于产生异戊烯基焦磷酸盐的不同酶。相关方法包括向宿主微生物中引入甲羟戊酸途径中的中间体和至少一个异源核酸序列，每个序列编码甲羟戊酸途径中的酶将中间体转化为异戊烯基焦磷酸。本发明还提供了用于实施该方法的核酸序列，酶，表达载体和转化的宿主细胞。

7. 发明授权

US07927794B2 Methods for identifying a biosynthetic pathway gene product 有权
标题翻译：识别生物合成途径基因产物的方法
公开(公告)号：US07927794B2
公开(公告)日：2011-04-19
申请号：US10573796
申请日：2004-09-29
申请人： Jay D. Keasling , Jack D. Newman , Douglas J. Pitera , Sydnor T. Withers, III , Keith Kinkead Reiling , Vincent J. J. Martin
发明人： Jay D. Keasling , Jack D. Newman , Douglas J. Pitera , Sydnor T. Withers, III , Keith Kinkead Reiling , Vincent J. J. Martin
IPC分类号： C12Q1/68 , C12N15/64 , C07H21/04
CPC分类号： C12N15/1079 , C12N15/52
摘要： The present invention provides isolated, genetically modified host cells, where a host cell is genetically modified with a nucleic acid that includes a nucleotide sequence encoding a biosynthetic pathway enzyme. Synthesis of the enzyme in the host cell results in conversion of a substrate for the enzyme into a biosynthetic pathway intermediate, which intermediate is produced in an amount effective to inhibit growth of the genetically modified host cell. The present invention further provides compositions and kits comprising a subject genetically modified host cell. Subject host cells are useful for identifying a gene product having activity in a biosynthetic pathway. The present invention further provides methods of identifying a gene product having activity in a biosynthetic pathway.
摘要翻译：本发明提供分离的遗传修饰的宿主细胞，其中宿主细胞用包含编码生物合成途径酶的核苷酸序列的核酸进行遗传修饰。在宿主细胞中合成酶导致酶的底物转化为生物合成途径中间体，该中间体以有效抑制转基因细胞生长的量产生。本发明还提供包含受试者遗传修饰的宿主细胞的组合物和试剂盒。受试宿主细胞可用于鉴定在生物合成途径中具有活性的基因产物。本发明还提供鉴定在生物合成途径中具有活性的基因产物的方法。

8. 发明授权

US08114645B2 Methods for increasing isoprenoid and isoprenoid precursor production by modulating fatty acid levels 有权
标题翻译：通过调节脂肪酸水平来增加类异戊二烯和类异戊二烯前体产生的方法
公开(公告)号：US08114645B2
公开(公告)日：2012-02-14
申请号：US12299004
申请日：2007-05-17
申请人： Douglas J. Pitera , Jack D. Newman , Jeffrey Lance Kizer , Jay D. Keasling , Brian F. Pfleger
发明人： Douglas J. Pitera , Jack D. Newman , Jeffrey Lance Kizer , Jay D. Keasling , Brian F. Pfleger
IPC分类号： C12N1/00 , C12N1/21 , C12P7/64
CPC分类号： C12P23/00
摘要： The present invention provides methods of increasing production of an isoprenoid or an isoprenoid precursor in a host cell, the methods generally involving modulating the level of activity of a fatty acid biosynthetic pathway enzyme in the host cell and/or culturing the host cell in a culture medium comprising a fatty acid or a compound that can be metabolized in a cell or broken down in the medium to yield a fatty acid and/or culturing the host cell in a culture medium having increased osmolarity.
摘要翻译：本发明提供了增加宿主细胞中类异戊二烯或类异戊二烯前体产生的方法，所述方法通常涉及调节宿主细胞中脂肪酸生物合成途径酶的活性水平和/或培养培养物中的宿主细胞包含可在细胞中代谢或在培养基中分解以产生脂肪酸和/或在具有增加的渗透压浓度的培养基中培养宿主细胞的脂肪酸或化合物的培养基。

9. 发明授权

US08257957B2 Production of isoprenoids and isoprenoid precursors 有权
标题翻译：类异戊二烯和类异戊二烯前体的生产
公开(公告)号：US08257957B2
公开(公告)日：2012-09-04
申请号：US12439812
申请日：2007-09-25
申请人： Jay D. Keasling , Farnaz Nowroozi , Douglas J. Pitera , Jennifer Anthony , Jack D. Newman , Larry Anthony
发明人： Jay D. Keasling , Farnaz Nowroozi , Douglas J. Pitera , Jennifer Anthony , Jack D. Newman , Larry Anthony
IPC分类号： C12N1/21 , C12N5/07 , C12N1/19
CPC分类号： C12N9/12 , C12N9/88
摘要： The present invention provides genetically modified host cells and use of same for producing isoprenoid compounds.
摘要翻译：本发明提供遗传修饰的宿主细胞及其用于产生类异戊二烯化合物的用途。

10. 发明授权

US07670825B2 Method for enhancing production of isoprenoid compounds 有权
标题翻译：增强异戊二烯化合物生产的方法
公开(公告)号：US07670825B2
公开(公告)日：2010-03-02
申请号：US11624094
申请日：2007-01-17
申请人： Jay D. Keasling , Jack D. Newman , Douglas J. Pitera
发明人： Jay D. Keasling , Jack D. Newman , Douglas J. Pitera
IPC分类号： C12N1/20 , C12N15/74 , C12N15/87 , C12P5/02 , C12P21/06 , C12P13/00 , A01N43/04
CPC分类号： C12P23/00 , C12N9/0006 , C12P9/00
摘要： The present invention provides methods of producing an isoprenoid or an isoprenoid precursor in a genetically modified host cell. The methods generally involve modulating the level of hydroxymethylglutaryl-CoA (HMG-CoA) in the cell, such that the level of HMG-CoA is not toxic to the cell and/or does not substantially inhibit cell growth, but is maintained at a level that provides for high-level production of mevalonate, IPP, and other downstream products of an isoprenoid or isoprenoid pathway, e.g., polyprenyl diphosphates and isoprenoid compounds. The present invention further provides genetically modified host cells that are suitable for use in a subject method. The present invention further provides recombinant nucleic acid constructs for use in generating a subject genetically modified host cell, including recombinant nucleic acid constructs comprising nucleotide sequences encoding one or more mevalonate pathway enzymes, and recombinant vectors (e.g., recombinant expression vectors) comprising same. The present invention further provides methods for identifying nucleic acids that encode HMG-CoA reductase (HMGR) variants that provide for relief of HMG-CoA accumulation-induced toxicity. The present invention farther provides methods for identifying agents that reduce intracellular accumulation of HMG-CoA.
摘要翻译：本发明提供在遗传修饰的宿主细胞中产生类异戊二烯或类异戊二烯前体的方法。方法通常涉及调节细胞中羟甲基戊二酰辅酶A（HMG-CoA）的水平，使得HMG-CoA的水平对细胞无毒性和/或基本上不抑制细胞生长，但维持在一个水平其规定了甲羟戊酸，IPP和类异戊二烯或类异戊二烯途径的其它下游产物的高水平生产，例如聚丙二醇二磷酸和类异戊二烯化合物。本发明还提供了适用于本发明方法的经遗传修饰的宿主细胞。本发明还提供用于产生受试者遗传修饰的宿主细胞的重组核酸构建体，包括重组核酸构建体，其包含编码一种或多种甲羟戊酸途径酶的核苷酸序列，以及包含其的重组载体（例如，重组表达载体）。本发明还提供了用于鉴定编码提供HMG-CoA积累诱导的毒性的HMG-CoA还原酶（HMGR）变体的核酸的方法。本发明进一步提供用于鉴定减少HMG-CoA的细胞内积累的试剂的方法。

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