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11. 发明授权

US08524485B2 Long chain omega-3 and omega-6 polyunsaturated fatty acid biosynthesis by expression of acyl-CoA lysophospholipid acyltransferases 有权
标题翻译：通过表达酰基辅酶A溶血磷脂酰基转移酶的长链ω-3和ω-6多不饱和脂肪酸生物合成
公开(公告)号：US08524485B2
公开(公告)日：2013-09-03
申请号：US12814764
申请日：2010-06-14
申请人： Narendra S. Yadav , Hongxiang Zhang , Quinn Qun Zhu
发明人： Narendra S. Yadav , Hongxiang Zhang , Quinn Qun Zhu
IPC分类号： C12N1/00 , C12N1/10 , C12N15/00 , C07H21/04 , A23D9/00
CPC分类号： C12N9/1029 , A21D2/165 , A23K20/158 , C12N9/00 , C12N9/13 , C12N9/93 , C12P7/6427 , C12P7/6472 , C12P7/6481
摘要： Methods for increasing C18 to C20 elongation conversion efficiency and/or Δ4 desaturation conversion efficiency in long-chain polyunsaturated fatty acid [“LC-PUFA”]-producing recombinant oleaginous microbial host cells are provided herein, based on over-expression of acyl-CoA:lysophospholipid acyltransferases [“LPLATs”] (e.g., Ale1, LPAAT, LPCAT). Production host cells and oils produced by the methods of the invention are also claimed.
摘要翻译：基于酰基辅酶A的过表达，本文提供了在长链多不饱和脂肪酸[“LC-PUFA”]生产重组油质微生物宿主细胞中提高C18至C20延伸转化效率和/或Delta4去饱和转化效率的方法：溶血磷脂酰基转移酶[“LPLAT”]（例如，Ale1，LPAAT，LPCAT）。还要求保护通过本发明方法生产的生产宿主细胞和油。

12. 发明申请

US20120052549A1 MUTANT HPGG MOTIF AND HDASH MOTIF DELTA-5 DESATURASES AND THEIR USE IN MAKING POLYUNSATURATED FATTY ACIDS 有权
标题翻译： MUTANT HPGG MOTIF和HDASH MOTIF DELTA-5 DESATURASES及其在制备聚氨酯脂肪酸中的应用
公开(公告)号：US20120052549A1
公开(公告)日：2012-03-01
申请号：US13218673
申请日：2011-08-26
申请人： Melissa D. Bosak , Michael W. Bostick , Hongxian He , Seung-Pyo Hong , Dana M. Walters Pollak , Pamela L. Sharpe , Yehong Jamie Wang , Zhixiong Xue , Narendra S. Yadav , Hongxiang Zhang , Quinn Qun Zhu
发明人： Melissa D. Bosak , Michael W. Bostick , Hongxian He , Seung-Pyo Hong , Dana M. Walters Pollak , Pamela L. Sharpe , Yehong Jamie Wang , Zhixiong Xue , Narendra S. Yadav , Hongxiang Zhang , Quinn Qun Zhu
IPC分类号： C12N9/02 , C12N5/10 , C12N1/19 , C07H21/04
CPC分类号： C12N9/001 , C12P7/6472 , C12Y103/01035
摘要： Mutant delta-5 desaturases, having the ability to convert dihomo-gamma-linolenic acid [DGLA; 20:3 omega-6] to arachidonic acid [ARA; 20:4 omega-6] and/or eicosatetraenoic acid [ETA; 20:4 omega-3] to eicosapentaenoic acid [EPA; 20:5 omega-3] and possessing at least one mutation within the HPGG (SEQ ID NO:7) motif of the cytochome b5-like domain and at least one mutation within the HDASH (SEQ ID NO:8) motif are disclosed. Isolated nucleic acid fragments and recombinant constructs comprising such fragments encoding delta-5 desaturases, along with a method of making long chain polyunsaturated fatty acids [“PUFAs”], are also disclosed.
摘要翻译：具有将dihomo-γ-亚麻酸转化的能力的变体delta-5去饱和酶[DGLA; 20：3ω-6]花生四烯酸[ARA; 20：4ω-6]和/或二十碳四烯酸[ETA; 20：4ω-3]至二十碳五烯酸[EPA; 20：5ω-3]，并且在细胞色素b5样结构域的HPGG（SEQ ID NO：7）基序和HDASH（SEQ ID NO：8）基序内的至少一个突变中具有至少一个突变。还公开了分离的核酸片段和包含编码Δ-5去饱和酶的片段的重组构建物，以及制备长链多不饱和脂肪酸[“PUFA”]的方法。

13. 发明申请

US20110086919A1 HIGH EICOSAPENTAENOIC ACID PRODUCING STRAINS OF YARROWIA LIPOLYTICA 有权
标题翻译：青蒿素的高效酸生产菌株
公开(公告)号：US20110086919A1
公开(公告)日：2011-04-14
申请号：US12893469
申请日：2010-09-29
申请人： Howard Glenn Damude , Peter John Gillies , Daniel Joseph Macool , Stephen K. Picataggio , Dana M. Walters Pollak , James John Ragghianti , Zhixiong Xue , Narendra S. Yadav , Hongxiang Zhang , Quinn Qun Zhu
发明人： Howard Glenn Damude , Peter John Gillies , Daniel Joseph Macool , Stephen K. Picataggio , Dana M. Walters Pollak , James John Ragghianti , Zhixiong Xue , Narendra S. Yadav , Hongxiang Zhang , Quinn Qun Zhu
IPC分类号： A61K31/202 , C12N1/15 , C12P7/64 , C07C57/03 , A61P9/00 , A61P3/10 , A61P19/02 , A61P1/00 , A61P17/02 , A61P19/10
CPC分类号： C12P7/6427 , A23D9/00 , A23K20/158 , A23L33/12 , A23V2002/00 , C12N1/16 , C12N9/0083 , C12N9/1029 , C12N15/52 , C12N15/746 , C12N15/815 , C12P7/6472 , A23V2250/187 , A23V2200/30
摘要： Engineered strains of the oleaginous yeast Yarrowia lipolytica capable of producing greater than 25% eicosapentaenoic acid (EPA, an ω-3 polyunsaturated fatty acid) in the total oil fraction are described. These strains comprise various chimeric genes expressing heterologous desaturases, elongases and acyltransferases and optionally comprise various native desaturase and acyltransferase knockouts to enable synthesis and high accumulation of EPA. Production host cells are claimed, as are methods for producing EPA within said host cells.
摘要翻译：描述了能够在总油馏分中产生大于25％二十碳五烯酸（EPA，ω-3多不饱和脂肪酸）的含油酵母解脂耶氏酵母解脂耶氏酵母菌的工程菌株。这些菌株包括表达异源去饱和酶，延伸酶和酰基转移酶的各种嵌合基因，并且任选地包含各种天然去饱和酶和酰基转移酶敲除，以使EPA能够合成和高度积累。要求生产宿主细胞，以及在所述宿主细胞内生产EPA的方法。

14. 发明申请

US20100041113A1 DELTA 6 DESATURASES AND THEIR USE IN MAKING POLYUNSATURATED FATTY ACIDS 有权
标题翻译： DELTA 6 DESATURASES及其在制备聚氨酯脂肪酸中的应用
公开(公告)号：US20100041113A1
公开(公告)日：2010-02-18
申请号：US12512429
申请日：2009-07-30
申请人： Narendra S. Yadav , Zhixiong Xue , Quinn Qun Zhu , Hongxiang Zhang
发明人： Narendra S. Yadav , Zhixiong Xue , Quinn Qun Zhu , Hongxiang Zhang
IPC分类号： C12P7/64 , C12N15/11 , C12N9/00 , C12N1/19 , C12N1/13 , C12N1/21 , C12N1/14
CPC分类号： C12N9/0083 , C12N9/0071 , C12P7/6427 , C12Y114/19003
摘要： The present invention relates to Δ6 desaturases, which have the ability to convert linoleic acid [“LA”; 18:2 ω-6] to γ-linolenic acid [“GLA”; 18:3 ω-6] and/or α-linolenic acid [“ALA”; 18:3 ω-3] to stearidonic acid [“STA”; 18:4 ω-3]. Isolated nucleic acid fragments and recombinant constructs comprising such fragments encoding Δ6 desaturases, along with methods of making long-chain polyunsaturated fatty acids [“PUFAs”] using these Δ6 desaturases in oleaginous yeast, are disclosed.
摘要翻译：本发明涉及具有转化亚油酸[“LA”; 18：2ω-6]至γ-亚麻酸[“GLA”; 18：3ω-6]和/或α-亚麻酸[“ALA”; 18：3ω-3]至十八碳四烯酸[“STA”; 18：4ω-3]。公开了分离的核酸片段和包含编码“Dgr”6去饱和酶的片段的重组构建体以及使用这些＆Dgr。6去饱和酶在含油酵母中制备长链多不饱和脂肪酸的方法。

15. 发明申请

US20100022647A1 HIGH ARACHIDONIC ACID PRODUCING STRAINS OF YARROWIA LIPOLYTICA 审中-公开
标题翻译：青蒿酸高产酸生产菌株
公开(公告)号：US20100022647A1
公开(公告)日：2010-01-28
申请号：US12512507
申请日：2009-07-30
申请人： Howard Glenn Damude , Peter John Gillies , Daniel Joseph Macool , Stephen K. Picataggio , Dana M. Walters Pollak , James John Ragghianti , Zhixiong Xue , Narendra S. Yadav , Hongxiang Zhang , Quinn Qun Zhu
发明人： Howard Glenn Damude , Peter John Gillies , Daniel Joseph Macool , Stephen K. Picataggio , Dana M. Walters Pollak , James John Ragghianti , Zhixiong Xue , Narendra S. Yadav , Hongxiang Zhang , Quinn Qun Zhu
IPC分类号： A61K31/20 , C12N1/19 , C07C57/04 , A23D9/00 , A23C23/00 , A23K1/00
CPC分类号： C12P7/6427 , A23D9/00 , A23K20/158 , A23L33/12 , A23V2002/00 , C12N1/16 , C12N9/0083 , C12N9/1029 , C12N15/52 , C12N15/746 , C12N15/815 , C12P7/6472 , A23V2250/187 , A23V2200/30
摘要： Engineered strains of the oleaginous yeast Yarrowia lipolytica capable of producing greater than 10% arachidonic acid (ARA, an ω-6 polyunsaturated fatty acid) in the total oil fraction are described. These strains comprise various chimeric genes expressing heterologous desaturases, elongases and acyltransferases, and optionally comprise various native desaturase and acyltransferase knockouts to enable synthesis and high accumulation of ARA. Production host cells are claimed, as are methods for producing ARA within said host cells.
摘要翻译：描述了能够在总油馏分中产生大于10％花生四烯酸（ARA，ω-6多不饱和脂肪酸）的含油酵母解脂耶氏酵母解脂耶氏酵母菌的工程菌株。这些菌株包含表达异源去饱和酶，延伸酶和酰基转移酶的各种嵌合基因，并且任选地包含各种天然去饱和酶和酰基转移酶敲除，以使ARA能够合成和高度积累。要求生产宿主细胞，以及在所述宿主细胞内产生ARA的方法。

16. 发明申请

US20130011846A1 DELTA 17 DESATURASE AND ITS USE IN MAKING POLYUNSATURATED FATTY ACIDS 审中-公开
标题翻译： DELTA 17去饱和及其在制备聚氨酯脂肪酸中的应用
公开(公告)号：US20130011846A1
公开(公告)日：2013-01-10
申请号：US13535775
申请日：2012-06-28
申请人： Narendra S. Yadav , Zhixiong Xue , Quinn Qun Zhu
发明人： Narendra S. Yadav , Zhixiong Xue , Quinn Qun Zhu
IPC分类号： C12N9/02 , C40B20/00 , C12Q1/68 , C12N15/53
CPC分类号： C12P7/6427 , C12N9/0083 , C12P7/6472
摘要： The present invention relates to Δ17 desaturases, which have the ability to convert ω-6 fatty acids into their ω-3 counterparts (i.e., conversion of arachidonic acid [20:4, ARA] to eicosapentaenoic acid [20:5, EPA]). Isolated nucleic acid fragments and recombinant constructs comprising such fragments encoding Δ17 desaturases along with a method of making long-chain polyunsaturated fatty acids (PUFAs) using these Δ17 desaturases in oleaginous yeast are disclosed.
摘要翻译：本发明涉及具有将ω-6脂肪酸转化成其ω-3对应物的能力（即将花生四烯酸[20:4，ARA]转化为二十碳五烯酸[20:5，EPA ]）。公开了分离的核酸片段和重组构建体，其包含编码＆amp; 17去饱和酶的这种片段以及使用这些在油性酵母中的这些＆Dgr.17去饱和酶制备长链多不饱和脂肪酸（PUFA）的方法。

17. 发明授权

US08241884B2 Δ17 desaturase and its use in making polyunsaturated fatty acids 有权
标题翻译：去饱和酶及其在制备多不饱和脂肪酸中的应用
公开(公告)号：US08241884B2
公开(公告)日：2012-08-14
申请号：US12469208
申请日：2009-05-20
申请人： Narendra S. Yadav , Zhixiong Xue , Quinn Qun Zhu
发明人： Narendra S. Yadav , Zhixiong Xue , Quinn Qun Zhu
IPC分类号： C12N1/16
CPC分类号： C12P7/6427 , C12N9/0083 , C12P7/6472
摘要： The present invention relates to Δ17 desaturases, which have the ability to convert ω-6 fatty acids into their ω-3 counterparts (i.e., conversion of arachidonic acid [20:4, ARA] to eicosapentaenoic acid [20:5, EPA]). Isolated nucleic acid fragments and recombinant constructs comprising such fragments encoding Δ17 desaturases along with a method of making long-chain polyunsaturated fatty acids (PUFAs) using these Δ17 desaturases in oleaginous yeast are disclosed.
摘要翻译：本发明涉及具有将ω-6脂肪酸转化成其ω-3对应物的能力（即将花生四烯酸[20:4，ARA]转化为二十碳五烯酸[20:5，EPA ]）。公开了分离的核酸片段和重组构建体，其包含编码＆amp; 17去饱和酶的这种片段以及使用这些在油性酵母中的这些＆Dgr.17去饱和酶制备长链多不饱和脂肪酸（PUFA）的方法。

18. 发明申请

US20090233346A1 PRODUCTION OF POLYUNSATURATED FATTY ACIDS IN OLEAGINOUS YEASTS 失效
公开(公告)号：US20090233346A1
公开(公告)日：2009-09-17
申请号：US12469467
申请日：2009-05-20
申请人： Stephen K. Picataggio , Narendra S. Yadav , Quinn Qun Zhu
发明人： Stephen K. Picataggio , Narendra S. Yadav , Quinn Qun Zhu
IPC分类号： C12N1/19 , C07C57/00
CPC分类号： C12N15/815 , C12P7/6427 , C12P7/6472
摘要： The present invention relates to methods for the production of ω-3 and/or ω-6 fatty acids in oleaginous yeast. Thus, desaturases and elongases able to catalyze the conversion of linoleic acid (LA) to γ-linolenic acid (GLA); α-linoleic acid (ALA) to stearidonic acid (STA); GLA to dihomo-γ-linoleic acid (DGLA); STA to eicosatetraenoic acid (ETA); DGLA to arachidonic acid (ARA); ETA to eicosapentaenoic acid (EPA); DGLA to ETA; EPA to docosapentaenoic acid (DPA); and ARA to EPA have been introduced into the genome of Yarrowia for synthesis of ARA and EPA.

19. 发明授权

US08637298B2 Optimized strains of yarrowia lipolytica for high eicosapentaenoic acid production 有权
标题翻译：优化的解脂耶氏酵母菌株用于高二十碳五烯酸生产
公开(公告)号：US08637298B2
公开(公告)日：2014-01-28
申请号：US12814815
申请日：2010-06-14
申请人： Seung-Pyo Hong , Pamela L. Sharpe , Zhixiong Xue , Narendra S. Yadav , Quinn Qun Zhu
发明人： Seung-Pyo Hong , Pamela L. Sharpe , Zhixiong Xue , Narendra S. Yadav , Quinn Qun Zhu
IPC分类号： C12N1/00
CPC分类号： C12N9/1029 , A21D2/165 , A23K20/158 , C12N9/00 , C12N9/13 , C12N9/93 , C12P7/6427 , C12P7/6472 , C12P7/6481
摘要： Described are engineered strains of the oleaginous yeast Yarrowia lipolytica capable of producing an oil comprising greater than 50 weight percent of eicosapentaenoic acid [“EPA”], an ω-3 polyunsaturated fatty acid, measured as a weight percent of total fatty acids [“% TFAs”] and having a ratio of at least 3.1 of EPA % TFAs, to linoleic acid, measured as % TFAs. These strains over-express at least one Δ9 elongase/Δ8 desaturase multizyme, in addition to other heterologous Δ9 elongases, Δ8 desaturases, Δ5 desaturases, Δ17 desaturases, Δ12 desaturases, C16/18 elongases, and optionally over-express diacylglycerol cholinephosphotransferases, malonyl CoA synthetases and/or acyl-CoA lysophospholipid acyltransferases. The expression of at least one peroxisome biogenesis factor protein is down-regulated. Methods for producing EPA within said host cells, oils obtained from the cells, and products therefrom are claimed.
摘要翻译：描述了能够产生包含大于50重量％的二十碳五烯酸[“EPA”]的油的油质酵母解脂耶氏酵母解脂耶氏酵母的工程菌株，其是以总脂肪酸的重量百分比测量的ω-3多不饱和脂肪酸[“％ TFAs“]，并且具有至少3.1％的EPA％TFA与比率为TFA的亚油酸的比率。除了其他异源Delta9延伸酶，Delta8去饱和酶，Δ5去饱和酶，Δ17去饱和酶，Δ12去饱和酶，C16 / 18延长酶和任选的过表达二酰基甘油胆碱磷酸转移酶，丙二酰辅酶A，这些菌株过表达至少一种Δ9延伸酶/Δδ去饱和酶多酶合成酶和/或酰基辅酶A溶血磷脂酰基转移酶。至少一种过氧化物酶体生物因子蛋白的表达下调。要求在所述宿主细胞内生产EPA的方法，从细胞获得的油及其产物。

20. 发明授权

US07879591B2 High eicosapentaenoic acid producing strains of Yarrowia lipolytica 有权
标题翻译：高二十碳五烯酸生产的解脂耶氏酵母菌株
公开(公告)号：US07879591B2
公开(公告)日：2011-02-01
申请号：US12485141
申请日：2009-06-16
申请人： Howard Glenn Damude , Zhixiong Xue , Narendra S. Yadav , Quinn Qun Zhu
发明人： Howard Glenn Damude , Zhixiong Xue , Narendra S. Yadav , Quinn Qun Zhu
IPC分类号： C12N1/16 , C12N9/10 , C12N15/70 , C12P21/06 , C07H21/04
CPC分类号： C12P7/6472 , A23K20/158 , A23L33/12 , A23V2002/00 , C12N9/0083 , C12N9/1029 , C12N15/52 , C12P7/6427 , A23V2250/187 , A23V2200/30
摘要： Lysophosphatidic acid acyltransferase [“LPAAT”] participates in the second step of oil biosynthesis and is expected to play a key role in altering the quantity of long-chain polyunsaturated fatty acids [“LC-PUFAs”] produced in oils of oleaginous organisms. An LPAAT isolated from Mortierella alpina [“MaLPAAT1”] that is suitable for use in the manufacture of oils enriched in LC-PUFAs in oleaginous organisms is disclosed. Most desirably, the substrate specificity of the instant MaLPAAT1 will be particularly useful to enable increased C18 to C20 elongation conversion efficiency and increased Δ4 desaturation conversion efficiency in recombinant host cells producing LC-PUFAs.
摘要翻译：溶血磷脂酰基转移酶[“LPAAT”]参与了油生物合成的第二步，预计在改变含油生物油中产生的长链多不饱和脂肪酸（“LC-PUFA”）的量方面起关键作用。公开了一种适用于制造含油生物中富含LC-PUFA的油的高山被孢霉[“MaLPAAT1”]分离的LPAAT。最令人满意的是，本发明的MaLPAAT1的底物特异性将特别有用，以便能够在产生LC-PUFA的重组宿主细胞中提高C18至C20延伸转换效率和增加和降低转化效率。

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