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1. 发明授权

US09234222B2 Microbial strains producing sphingoid bases or derivatives thereof 有权
标题翻译：产生螺旋体碱或其衍生物的微生物菌株
公开(公告)号：US09234222B2
公开(公告)日：2016-01-12
申请号：US11666863
申请日：2005-11-07
申请人： Marco Alexander Van Den Berg , Steffen Schaffer
发明人： Marco Alexander Van Den Berg , Steffen Schaffer
IPC分类号： C12P13/00 , C12P13/02
CPC分类号： C12P13/001 , C12P13/02
摘要： The present invention provides microbial strains, in particular yeast strains, that produce at least 0.1 mg per g biomass dry weight of a sphingoid base. The present invention further provides a method to obtain sphingoid base-producing microbial strains comprising incubating a population of microbial cells in the presence of a suitable concentration of a toxin, selecting cells that are resistant against said toxin, and isolating cells out of the toxin-resistant cell population that produce at least 0.1 mg per g biomass dry weight of the sphingoid base of Formula I. Optionally, the method further comprises subjecting a population of toxin-resistant microbial cells that produce at least 0.1 mg per g biomass dry weight of the sphingoid base of Formula I to DNA-mediated transformation with a polynucleotide encoding an enzyme of the sphingolipid metabolic pathway. The present invention further provides a polypeptide having dihydroceramide desaturase activity obtainable form Pichia ciferrii.
摘要翻译：本发明提供了生产至少0.1mg / g生物量干重的类鞘氨醇碱的微生物菌株，特别是酵母菌株。本发明还提供一种获得产生类鞘氨醇碱的微生物菌株的方法，包括在合适浓度的毒素存在下孵育一群微生物细胞，选择对所述毒素具有抗性的细胞，以及从毒素 - 产生至少0.1mg / g生物质干重的式I的类鞘氨醇碱。任选地，所述方法还包括使生产至少0.1mg / g生物量干重的毒素抗性微生物细胞群体式I的鞘氨醇类碱基与编码鞘脂代谢途径酶的多核苷酸进行DNA介导的转化。本发明还提供一种具有从毕赤酵母（Pichia ciferrii）获得的二氢神经酰胺去饱和酶活性的多肽。

2. 发明申请

US20080299625A1 Microbial Strains Producing Sphingoid Bases or Derivatives Thereof 有权
标题翻译：产生鞘氨醇碱或其衍生物的微生物菌株
公开(公告)号：US20080299625A1
公开(公告)日：2008-12-04
申请号：US11666863
申请日：2005-11-07
申请人： Marco Alexander Van Den Berg , Steffen Schaffer
发明人： Marco Alexander Van Den Berg , Steffen Schaffer
IPC分类号： C12P13/00 , C12N1/19 , C12N15/87 , C12N9/00 , C12N15/11
CPC分类号： C12P13/001 , C12P13/02
摘要： The present invention provides microbial strains, in particular yeast strains, that produce at least 0.1 mg per g biomass dry weight of a sphingoid base. The present invention further provides a method to obtain sphingoid base-producing microbial strains comprising incubating a population of microbial cells in the presence of a suitable concentration of a toxin, selecting cells that are resistant against said toxin, and isolating cells out of the toxin-resistant cell population that produce at least 0.1 mg per g biomass dry weight of the sphingoid base of Formula I. Optionally, the method further comprises subjecting a population of toxin-resistant microbial cells that produce at least 0.1 mg per g biomass dry weight of the sphingoid base of Formula I to DNA-mediated transformation with a polynucleotide encoding an enzyme of the sphingolipid metabolic pathway. The present invention further provides a polypeptide having dihydroceramide desaturase activity obtainable form Pichia ciferrii.
摘要翻译：本发明提供了生产至少0.1mg / g生物量干重的类鞘氨醇碱的微生物菌株，特别是酵母菌株。本发明还提供一种获得产生类鞘氨醇碱的微生物菌株的方法，包括在合适浓度的毒素存在下孵育一群微生物细胞，选择对所述毒素具有抗性的细胞，以及从毒素 - 产生至少0.1mg / g生物质干重的式I的类鞘氨醇碱。任选地，所述方法还包括使生产至少0.1mg / g生物量干重的毒素抗性微生物细胞群体式I的鞘氨醇类碱基与编码鞘脂代谢途径酶的多核苷酸进行DNA介导的转化。本发明还提供一种具有从毕赤酵母（Pichia ciferrii）获得的二氢神经酰胺去饱和酶活性的多肽。

3. 发明授权

US08372595B2 Method for obtaining a microbial strain for production of sphingoid bases 有权
标题翻译：获得用于生产类鞘氨醇碱的微生物菌株的方法
公开(公告)号：US08372595B2
公开(公告)日：2013-02-12
申请号：US12300397
申请日：2007-05-11
申请人： Steffen Schaffer , Marco Alexander Van Den Berg , Daniel Boergel , Thomas Hueller
发明人： Steffen Schaffer , Marco Alexander Van Den Berg , Daniel Boergel , Thomas Hueller
IPC分类号： G01N33/53 , C12P7/18 , C12N1/00
CPC分类号： C12N9/80 , A61K8/68 , A61K2800/86 , A61Q19/00 , C12N9/0071 , C12N9/1029
摘要： The present invention provides genetically engineered microbial strains, in particular genetically engineered yeast strains, that produce at least 0.5 mg per g CDW of a sphingoid base according to Formula I or a salt or ester thereof. The present invention provides a method to obtain genetically engineered microbial strains producing at least 0.5 mg per g CDW of a sphingoid base according to Formula I or a salt or ester thereof. The method comprises the steps of: a) increasing the expression of a polynucleotide encoding an enzyme having ceramide synthase activity and/or an enzyme having ceramidase activity, the latter being capable of preferentially, or even specifically, hydrolyzing ceramides containing a sphingoid base according to Formula I, and/or b) decreasing the expression of a polynucleotide encoding an enzyme having sphingolipid Δ8-desaturase activity and/or an enzyme having ceramidase activity, the latter being capable of preferentially, or even specifically, hydrolyzing ceramides containing phytosphingosine or dihydrosphingosine as sphingoid base, and isolating strains with the required productivity.
摘要翻译：本发明提供基因工程微生物菌株，特别是遗传工程酵母菌株，其产生至少0.5mg / g CDW的根据式I的鞘氨醇碱或其盐或酯。本发明提供了一种获得基因工程的微生物菌株的方法，其产生至少0.5mg / g CDW的根据式I的鞘氨醇碱或其盐或酯。该方法包括以下步骤：a）增加编码具有神经酰胺合成酶活性的酶的多核苷酸和/或具有神经酰胺酶活性的酶的表达，后者能够优先或甚至具体地水解含有类鞘氨醇碱的神经酰胺根据式I，和/或b）减少编码具有鞘脂和Dgr.8-去饱和酶活性的酶的多核苷酸的表达和/或具有神经酰胺酶活性的酶，后者能够优先或甚至具体地水解含有植物鞘氨醇的神经酰胺或二氢鞘氨醇作为鞘氨醇碱，并以所需的生产力分离菌株。

4. 发明申请

US20100190219A1 PRODUCTION OF SPHINGOID BASES USING GENETICALLY ENGINEERED MICROBIAL STRAINS 有权
标题翻译：使用遗传工程微生物菌株生产刺槐根
公开(公告)号：US20100190219A1
公开(公告)日：2010-07-29
申请号：US12300397
申请日：2007-05-11
申请人： Steffen Schaffer , Marco Alexander Van Den Berg , Daniel Boergel , Thomas Hueller
发明人： Steffen Schaffer , Marco Alexander Van Den Berg , Daniel Boergel , Thomas Hueller
IPC分类号： C12P13/02 , C12N1/00 , C12N15/74 , C12N9/00 , C12N9/02 , C12N9/78
CPC分类号： C12N9/80 , A61K8/68 , A61K2800/86 , A61Q19/00 , C12N9/0071 , C12N9/1029
摘要： The present invention provides genetically engineered microbial strains, in particular genetically engineered yeast strains, that produce at least 0.5 mg per g CDW of a sphingoid base according to Formula I or a salt or ester thereof. The present invention provides a method to obtain genetically engineered microbial strains producing at least 0.5 mg per g CDW of a sphingoid base according to Formula I or a salt or ester thereof. The method comprises the steps of: a) increasing the expression of a polynucleotide encoding an enzyme having ceramide synthase activity and/or an enzyme having ceramidase activity, the latter being capable of preferentially, or even specifically, hydrolyzing ceramides containing a sphingoid base according to Formula I, and/or b) decreasing the expression of a polynucleotide encoding an enzyme having sphingolipid Δ8-desaturase activity and/or an enzyme having ceramidase activity, the latter being capable of preferentially, or even specifically, hydrolyzing ceramides containing phytosphingosine or dihydrosphingosine as sphingoid base, and isolating strains with the required productivity.
摘要翻译：本发明提供基因工程微生物菌株，特别是遗传工程酵母菌株，其产生至少0.5mg / g CDW的根据式I的鞘氨醇碱或其盐或酯。本发明提供了一种获得基因工程的微生物菌株的方法，其产生至少0.5mg / g CDW的根据式I的鞘氨醇碱或其盐或酯。该方法包括以下步骤：a）增加编码具有神经酰胺合成酶活性的酶的多核苷酸和/或具有神经酰胺酶活性的酶的表达，后者能够优先或甚至具体地水解含有类鞘氨醇碱的神经酰胺根据式I，和/或b）减少编码具有鞘脂和Dgr.8-去饱和酶活性的酶的多核苷酸的表达和/或具有神经酰胺酶活性的酶，后者能够优先或甚至具体地水解含有植物鞘氨醇的神经酰胺或二氢鞘氨醇作为鞘氨醇碱，并以所需的生产力分离菌株。

5. 发明授权

US08697364B2 High throughput transfection of filamentous fungi 有权
标题翻译：高通量转染丝状真菌
公开(公告)号：US08697364B2
公开(公告)日：2014-04-15
申请号：US12306314
申请日：2007-06-25
申请人： Marco Alexander Van Den Berg , Bianca Elisabeth Maria Gielesen , Adriana Marina Riemens
发明人： Marco Alexander Van Den Berg , Bianca Elisabeth Maria Gielesen , Adriana Marina Riemens
IPC分类号： C12Q1/68
CPC分类号： C12N15/80 , C12P21/02
摘要： The present invention provides a method for the transfection of filamentous fungal cells, comprising providing a multitude of containers, filling into each container an amount of polymer needed for the transfection, filling the cells to be transfected as well as an aqueous solution of transfection reagent into each of the containers, incubating the resulting mixture, removing the transfection reagent from the incubated mixture; and selecting the cells which have been transformed, characterized in that the total volume of the incubating mixture is less than 1 ml per container. Furthermore, the present invention provides the use of transformed filamentous fungal cells for the production of proteins or metabolites.
摘要翻译：本发明提供丝状真菌细胞的转染方法，包括提供多个容器，向每个容器填充一定量的转染所需的聚合物，将待转染的细胞以及转染试剂的水溶液加入每个容器，孵育所得混合物，从培养的混合物中除去转染试剂; 并选择已经转化的细胞，其特征在于培养混合物的总体积小于每个容器1ml。此外，本发明提供了转化的丝状真菌细胞用于生产蛋白质或代谢物的用途。

6. 发明申请

US20100048938A1 FERMENTATION OF PRAVASTATIN 审中-公开
标题翻译： PRAVASTATIN的发酵
公开(公告)号：US20100048938A1
公开(公告)日：2010-02-25
申请号：US12305591
申请日：2007-06-19
申请人： Marco Alexander Van Den Berg , Bernard Meijrink
发明人： Marco Alexander Van Den Berg , Bernard Meijrink
IPC分类号： C07C69/76 , C12N1/15 , C12P1/02 , C12P7/62
CPC分类号： C12N15/52 , C12N9/0071 , C12P7/62
摘要： The present invention provides a microorganism containing a compactin biosynthesis gene and a gene for conversion of compactin into pravastatin. In a preferred example, said compactin biosynthesis gene is mIcA and/or mIcB and/or mIcC and/or mIcD and/or mIcE and/or mIcF and/or mIcG and/or mIcH and/or mIcR and said gene for conversion of compactin into pravastatin is a hydroxylase gene. Furthermore, the present invention provides a method for producing a compound of interest such as a statin. In a preferred example said statin is pravastatin.
摘要翻译：本发明提供一种含有贝伐菌素生物合成基因的微生物和将其转化为普伐他汀的基因。在优选的实施例中，所述紧密连接蛋白生物合成基因是mIcA和/或mIcB和/或mIcC和/或mIcD和/或mIcE和/或mIcF和/或mIcG和/或mIcH和/或mIcR以及所述用于转化成熟物的基因普伐他汀是一种羟化酶基因。此外，本发明提供了一种感兴趣的化合物如他汀类药物的制备方法。在优选的实例中，他汀类是普伐他汀。

7. 发明申请

US20100036174A1 BUTANOL PRODUCTION IN A EUKARYOTIC CELL 审中-公开
标题翻译：丁醇生产在一个欧洲细胞
公开(公告)号：US20100036174A1
公开(公告)日：2010-02-11
申请号：US12447740
申请日：2007-10-30
申请人： Lourina Madeleine Raamsdonk , Wilhelmus Theodorus Antonius Maria De Laat , Marco Alexander Van Den Berg
发明人： Lourina Madeleine Raamsdonk , Wilhelmus Theodorus Antonius Maria De Laat , Marco Alexander Van Den Berg
IPC分类号： C12P7/16 , C12N1/16 , C07C31/12
CPC分类号： C12P7/16 , C12N1/18 , C12N9/0006 , C12N9/0008 , C12N9/001 , C12N9/1029 , C12N9/88 , C12Y102/0101 , C12Y103/99002 , C12Y203/01009 , Y02E50/10
摘要： The present invention relates to a transformed eukaryotic cell comprising one or more nucleotide sequence(s) encoding acetyl-CoA acetyltransferase, 3-hydroxybutyryl-CoA dehydrogenase, 3-hydroxybutyryl-CoA dehydratase, butyryl-CoA dehydrogenase, alcohol dehydrogenase or acetaldehyde dehydrogenase and/or NAD(P)H-dependent butanol dehydrogenase, whereby the nucleotide sequence(s) upon transformation of the cell confer(s) the cell the ability to produce butanol. The invention also relates to a process for the production of butanol.
摘要翻译：本发明涉及包含编码乙酰辅酶A乙酰转移酶，3-羟基丁酰辅酶A脱氢酶，3-羟基丁酰辅酶A脱水酶，丁酰辅酶A脱氢酶，醇脱氢酶或乙醛脱氢酶的一个或多个核苷酸序列的转化真核细胞和/ 或NAD（P）H依赖性丁醇脱氢酶，由此转化细胞后的核苷酸序列赋予细胞产生丁醇的能力。本发明还涉及生产丁醇的方法。

8. 发明申请

US20110165585A1 MULTI-SPECIES POLYNUCLEOTIDE CONTROL SEQUENCES 审中-公开
标题翻译：多品种多核苷酸控制序列
公开(公告)号：US20110165585A1
公开(公告)日：2011-07-07
申请号：US12997330
申请日：2009-06-11
申请人： Marco Alexander Van Den Berg
发明人： Marco Alexander Van Den Berg
IPC分类号： C12P1/00 , C07H21/00 , C12N15/63 , C12N1/00 , C12Q1/68 , C12P21/00 , C12N15/00
CPC分类号： C12N15/63 , C12N15/70 , C12N15/75 , C12N15/80 , C12N15/81
摘要： The present invention relates to polynucleotide sequences which enable a polynucleotide control sequence, such as a promoter, to direct expression in a wide range of industrially relevant species, both prokaryotes and eukaryotes. When the polynucleotide sequences of the invention are applied in combination with selection marker genes it is possible to perform selectable cloning in a laboratory host and use the same construct in the final host
摘要翻译：本发明涉及能够使多核苷酸控制序列（例如启动子）在多种工业相关物种（原核生物和真核生物）中引导表达的多核苷酸序列。当本发明的多核苷酸序列与选择标记基因组合应用时，可以在实验室宿主中进行可选择克隆，并在最终宿主中使用相同的构建体

9. 发明申请

US20110091944A1 ADIPATE (ESTER OR THIOESTER) SYNTHESIS 有权
标题翻译：综合（ESTER或THIOESTER）合成
公开(公告)号：US20110091944A1
公开(公告)日：2011-04-21
申请号：US12921547
申请日：2009-03-11
申请人： Liang Wu , Stefaan Marie Andre De Wildeman , Marco Alexander Van Den Berg , Axel Christoph Trefzer
发明人： Liang Wu , Stefaan Marie Andre De Wildeman , Marco Alexander Van Den Berg , Axel Christoph Trefzer
IPC分类号： C12P7/62 , C12P11/00 , C12P7/44 , C12P7/26 , C12P13/00 , C12P17/10 , C12N1/00
CPC分类号： C12P7/44 , C12N15/70 , C12P7/62 , C12P17/10
摘要： The present invention relates to a method for preparing an adipate ester or thioester. The invention further relates to a method for preparing adipic acid from said ester or thioester. Further the invention provides a number of methods for preparing an intermediate for said ester or thioester. Further the invention relates to a method for preparing 6-amino caproic acid (6-ACA), a method for preparing 5-formyl valeric acid (5-FVA), and a method for preparing caprolactam. Further, the invention relates to a host cell for use in a method according to the invention.
摘要翻译：本发明涉及一种制备己二酸酯或硫酯的方法。本发明还涉及从所述酯或硫酯制备己二酸的方法。此外，本发明提供了许多用于制备所述酯或硫酯的中间体的方法。本发明还涉及制备6-氨基己酸（6-ACA）的方法，5-甲酰戊酸（5-FVA）的制备方法和己内酰胺的制备方法。此外，本发明涉及用于根据本发明的方法的宿主细胞。

10. 发明申请

US20110054193A1 STATIN PRODUCTION 审中-公开
标题翻译：生产生产
公开(公告)号：US20110054193A1
公开(公告)日：2011-03-03
申请号：US12989540
申请日：2009-04-28
申请人： Marco Alexander Van Den Berg , Marcus Hans
发明人： Marco Alexander Van Den Berg , Marcus Hans
IPC分类号： C07D309/30 , C12N9/02 , C07H21/04 , C12P17/06 , C12P7/64 , C12N1/15 , C12N1/19 , C07C69/34
CPC分类号： A61K31/366 , C12N9/0006 , C12P7/42 , C12P7/62 , C12P17/06
摘要： The present invention relates to a polypeptide with HMG-CoA reductase activity, to its polynucleotide congener and to a method for the production of a statin comprising over expression of said polypeptide.
摘要翻译：本发明涉及具有HMG-CoA还原酶活性的多肽，其多核苷酸同系物和包含过表达所述多肽的他汀类药物的制备方法。

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