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1. 发明申请

WO2008000632A1 A METHOD FOR ACHIEVING IMPROVED POLYPEPTIDE EXPRESSION 审中-公开
标题翻译：实现改进的多肽表达的方法
公开(公告)号：WO2008000632A1
公开(公告)日：2008-01-03
申请号：PCT/EP2007/055943
申请日：2007-06-15
申请人： DSM IP Assets B.V. , ROUBOS, Johannes, Andries , PEIJ, VAN, Noël Nicolaas Maria Elisabeth
发明人： ROUBOS, Johannes, Andries , PEIJ, VAN, Noël Nicolaas Maria Elisabeth
IPC分类号： C12N15/67
CPC分类号： C12N15/67 , C12N9/242 , C12N9/92 , C12N15/80 , C12N15/81 , C12N2800/22
摘要： The present invention relates to methods of optimization of a protein coding sequences for expression in a given host cell. The methods apply genetic algorithms to optimise single codon fitness and/or codon pair fitness sequences coding for a predetermined amino acid sequence. In the algorithm generation of new sequence variants and subsequent selection of fitter variants is reiterated until the variant coding sequences reach a minimum value for single codon fitness and/or codon pair fitness. The invention also relates to a computer comprising a processor and memory, the processor being arranged to read from and write into the memory, the memory comprising data and instructions arranged to provide the processor with the capacity to perform the genetic algorithms for optimisation of single codon fitness and/or codon pair fitness. The invention further relates to nucleic acids comprising a coding sequence for a predetermined amino acid sequence, the coding sequence being optimised with respect to single codon fitness and/or codon pair fitness for a given host in the methods of the invention, to host cells comprising such nucleic acids and to methods for producing polypeptides and other fermentation products in which these host cells are used.
摘要翻译：本发明涉及用于在给定宿主细胞中表达的蛋白质编码序列的优化方法。该方法应用遗传算法来优化编码预定氨基酸序列的单个密码子适合度和/或密码子对适应性序列。在算法中重复生成新的序列变体并随后选择拟合变体，直到变体编码序列达到单个密码子适应度和/或密码子对适应度的最小值。本发明还涉及一种包括处理器和存储器的计算机，所述处理器被布置为从存储器读取和写入存储器，所述存储器包括数据和指令，其被布置为向处理器提供执行遗传算法以优化单个密码子的能力健身和/或密码子对健身。本发明还涉及包含用于预定氨基酸序列的编码序列的核酸，所述编码序列针对本发明方法中给定宿主的单个密码子适合度和/或密码子对适应性优化至包含这种核酸以及用于产生其中使用这些宿主细胞的多肽和其它发酵产物的方法。

2. 发明申请

WO2010102982A1 METHOD FOR IMPROVING THE YIELD OF A POLYPEPTIDE 审中-公开
标题翻译：改善多肽的含量的方法
公开(公告)号：WO2010102982A1
公开(公告)日：2010-09-16
申请号：PCT/EP2010/052918
申请日：2010-03-08
申请人： DSM IP Assets B.V. , LAAN, VAN DER, Jan Metske , WU, Liang , ROUBOS, Johannes, Andries , PARENICOVA, Lucie , LOS, Alrik Pieter , PEIJ, VAN, Noël Nicolaas Maria Elisabeth , PEL, Herman Jan
发明人： LAAN, VAN DER, Jan Metske , WU, Liang , ROUBOS, Johannes, Andries , PARENICOVA, Lucie , LOS, Alrik Pieter , PEIJ, VAN, Noël Nicolaas Maria Elisabeth , PEL, Herman Jan
IPC分类号： C12P21/02 , C12N15/67
CPC分类号： C12P21/02
摘要： The present invention relates to a method for improving protein yield. The method comprises modifying the value of a set of relevant protein features to fall within an optimal range or to become more close to an optimal value for one or more protein features in the eukaryotic host.
摘要翻译：本发明涉及提高蛋白质产量的方法。该方法包括将一组相关蛋白质特征的值修改为落入最佳范围内，或者变得更接近于真核宿主中的一种或多种蛋白质特征的最佳值。

3. 发明申请

WO2007063133A2 NOVEL GENES USEFUL FOR THE INDUSTRIAL PRODUCTION OF CITRIC ACID 审中-公开
标题翻译：用于工业生产柠檬酸的新型基因
公开(公告)号：WO2007063133A2
公开(公告)日：2007-06-07
申请号：PCT/EP2006/069218
申请日：2006-12-01
申请人： DSM IP ASSETS B.V. , BAUWELEERS, Hugo Marc Karel , GROESENEKEN, Dominique Robert , PEIJ, VAN, Noël Nicolaas Maria Elisabeth
发明人： BAUWELEERS, Hugo Marc Karel , GROESENEKEN, Dominique Robert , PEIJ, VAN, Noël Nicolaas Maria Elisabeth
IPC分类号： C07K14/38 , C12P7/48
CPC分类号： C12P7/48 , C07K14/38
摘要： The present invention relates to newly identified genes that encode proteins that are involved in the (bio)synthesis of citric acid. The invention also features polynucleotides comprising the full-length polynucleotide sequences of the novel genes and fragments thereof, the novel polypeptides encoded by the polynucleotides and fragments thereof, as well as their functional equivalents. The present invention also relates to the use of said polynucleotides and polypeptides as biotechnological tools in the production of citric acid from microorganisms, whereby a modification of said polynucleotides and/or encoded polypeptides has a direct or indirect impact on yield, production, and/or efficiency of production of the fermentation product in said microorganism. Also included are methods/processes of using the polynucleotides and modified polynucleotide sequences to transform host microorganisms. The invention also relates to genetically engineered microorganisms and their use for production of citric acid.
摘要翻译：本发明涉及编码参与柠檬酸（生物）合成的蛋白质的新鉴定的基因。本发明还涉及包含新基因及其片段的全长多核苷酸序列的多核苷酸，由多核苷酸及其片段编码的新多肽及其功能等同物。本发明还涉及所述多核苷酸和多肽作为生物技术工具在从微生物生产柠檬酸中的用途，其中所述多核苷酸和/或编码多肽的修饰对产量，产量和/或所述微生物中发酵产物的生产效率。还包括使用多核苷酸和修饰的多核苷酸序列转化宿主微生物的方法/方法。本发明还涉及基因工程微生物及其生产柠檬酸的用途。

4. 发明申请

WO2011009700A1 IMPROVED HOST CELL FOR THE PRODUCTION OF A COMPOUND OF INTEREST 审中-公开
标题翻译：改进的生物化合物的主体细胞
公开(公告)号：WO2011009700A1
公开(公告)日：2011-01-27
申请号：PCT/EP2010/059390
申请日：2010-07-01
申请人： DSM IP ASSETS B.V. , PEIJ, VAN, Noël Nicolaas Maria Elisabeth , PEL, Herman Jan , WENZEL, Thibaut, José , RIEMENS, Adriana Marina , LANGE, DE, Ilse
发明人： PEIJ, VAN, Noël Nicolaas Maria Elisabeth , PEL, Herman Jan , WENZEL, Thibaut, José , RIEMENS, Adriana Marina , LANGE, DE, Ilse
IPC分类号： C12N15/81 , C12N15/00 , C12N1/16 , C12N15/56 , C12N9/60
CPC分类号： C12P21/00 , A01K2267/01 , C12N9/2428 , C12N15/80 , C12N15/8509 , C12N15/902
摘要： The present invention relates to a recombinant host cell for the production of a compound of interest. The invention further relates to a method for the production of such host cell. The invention further relates to the production of a compound of interest. The invention further relates to isolated polynucleotides and vectors and host cells comprising said polynucleotides.
摘要翻译：本发明涉及用于生产感兴趣的化合物的重组宿主细胞。本发明还涉及生产这种宿主细胞的方法。本发明还涉及生产感兴趣的化合物。本发明还涉及分离的多核苷酸和包含所述多核苷酸的载体和宿主细胞。

5. 发明申请

WO2008053018A3 IMPROVED PRODUCTION OF SECRETED PROTEINS BY FILAMENTOUS FUNGI 审中-公开
公开(公告)号：WO2008053018A3
公开(公告)日：2008-05-08
申请号：PCT/EP2007/061765
申请日：2007-10-31
申请人： DSM IP ASSETS B.V. , SAGT, Cornelis, Maria, Jacobus , VERRIPS, Cornelis Theodorus , MULLER, Walraven Henry , PEIJ, VAN, Noël Nicolaas Maria Elisabeth
发明人： SAGT, Cornelis, Maria, Jacobus , VERRIPS, Cornelis Theodorus , MULLER, Walraven Henry , PEIJ, VAN, Noël Nicolaas Maria Elisabeth
IPC分类号： C12N15/80 , C07K14/37
摘要： The present invention relates to a method to improve the secretion of a protein of interest by a filamentous fungal cell comprising inducing a phenotype in the cell selected from the group consisting of a lowered ERAD, an elevated UPR that does not induce an elevated ERAD, wherein ERAD preferably is lowered. The invention further relates to the filamentous fungal cell comprising the phenotype described above. The invention also relates to polynucleotides and polypeptides whose expression can be modulated in the filamentous fungal cell to obtain the above-described phenotype.

6. 发明申请

WO2007062936A2 DNA BINDING SITE OF A TRANSCRIPTIONAL ACTIVATOR USEFUL IN GENE EXPRESSION 审中-公开
标题翻译：转录激活因子基因表达的DNA结合位点
公开(公告)号：WO2007062936A2
公开(公告)日：2007-06-07
申请号：PCT/EP2006/067734
申请日：2006-10-24
申请人： DSM IP ASSETS B.V. , PARENICOVA, Lucie , PEIJ, VAN, Noël Nicolaas Maria Elisabeth
发明人： PARENICOVA, Lucie , PEIJ, VAN, Noël Nicolaas Maria Elisabeth
IPC分类号： C12N15/80
CPC分类号： C12N15/80
摘要： We have discovered DNA binding sites which are specifically recognized by PrtT, a transcriptional activator for protease genes. The DNA binding site can be defined structurally by a consensus nucleotide sequence and functionally by PrtT's ability to regulate transcriptional activation through that sequence. Both PrtT and its cognate DNA binding site (i.e., the nucleotide sequence in each promoter that is recognized by PrtT) can be used in a gene expression system. Possession of only a PrtT transcriptional activator is insufficient, its cognate DNA binding site is necessary for recognition by PrtT (i.e., binding to the site and activating transcription under appropriate conditions). A functional site, such as one obtained from a wild-type fungal gene, will confer PrtT- dependent transcriptional activation on 3'-downstream sequences. A mutation of a wild- type promoter that results in a non-functional site will abolish PrtT-dependent transcriptional activation of 3'-downstream sequences. A mutation of a wild-type promoter that results in a more functional site will enhance PrtT-dependent transcriptional activation of 3'-downstream sequences.
摘要翻译：我们发现了特异性被蛋白酶基因转录激活因子PrtT识别的DNA结合位点。 DNA结合位点可以由共有核苷酸序列在结构上定义，并在功能上由PrtT通过该序列调节转录激活的能力来定义。 PrtT及其同源DNA结合位点（即每个启动子中被PrtT识别的核苷酸序列）都可用于基因表达系统。仅拥有PrtT转录激活因子是不够的，其同源DNA结合位点对于PrtT识别是必需的（即，在适当条件下与该位点结合并激活转录）。功能位点，例如从野生型真菌基因获得的位点，将赋予3'-下游序列上PrtT依赖性转录激活。导致非功能性位点的野生型启动子的突变将消除3'-下游序列的PrtT依赖性转录激活。导致更多功能位点的野生型启动子的突变将增强3'下游序列的PrtT依赖性转录激活。

7. 发明申请

WO2005100573A3 FUNGAL PROMOTERS FOR EXPRESSING A GENE IN A FUNGAL CELL 审中-公开
公开(公告)号：WO2005100573A3
公开(公告)日：2005-10-27
申请号：PCT/EP2005/051696
申请日：2005-04-18
申请人： DSM IP ASSETS B.V. , WENZEL, Thibaut, José , PEIJ, VAN, Noël Nicolaas Maria Elisabeth , STAM, Hein
发明人： WENZEL, Thibaut, José , PEIJ, VAN, Noël Nicolaas Maria Elisabeth , STAM, Hein
IPC分类号： C12N15/80 , C07K14/47
摘要： The present invention relates to isolated fungal promoter DNA sequences, to DNA constructs, vectors, and fungal host cells comprising these promoters in operative association with coding sequences encoding polypeptides. The present invention also relates to methods for expressing a gene and/or producing a polypeptide using the new promoters isolated. The present invention also relates to methods for altering the transcription level and/or regulation of an endogenous gene using the new promoter of the invention.

8. 发明申请

WO2006040312A3 FUNGAL TRANSCRIPTIONAL ACTIVATORS USEFUL IN METHODS FOR PRODUCING A POLYPEPTIDE 审中-公开
公开(公告)号：WO2006040312A3
公开(公告)日：2006-04-20
申请号：PCT/EP2005/055145
申请日：2005-10-11
申请人： DSM IP ASSETS B.V. , PEIJ, VAN, Noël Nicolaas Maria Elisabeth , PARENICOVA, Lucie
发明人： PEIJ, VAN, Noël Nicolaas Maria Elisabeth , PARENICOVA, Lucie
IPC分类号： C12N15/31 , C12N15/67 , C07K14/37
摘要： The present invention relates to functional cDNA and genomic sequences encoding PrtT proteins, which have transcriptional activity on a protease promoter, to PrtT proteins and to their use. The invention further relates to two distinct types of filamentous fungal cells. Filamentous fungal cells are transformed to over-express these PrtT proteins: this type of filamentous fungus will be highly suited as protease producer. Alternatively, the endogenous prtT genes of filamentous fungal cells are inactivated: this type of filamentous fungus is highly suited for the production of any polypeptide native or not which is highly sensitive for protease degradation. The PrtT proteins of the invention provide means for identification of functional homologues in other species.

9. 发明申请

WO2005123763A1 PRODUCTION OF POLYPEPTIDES BY IMPROVED SECRETION 审中-公开
标题翻译：通过改进分泌生产多糖
公开(公告)号：WO2005123763A1
公开(公告)日：2005-12-29
申请号：PCT/EP2005/052805
申请日：2005-06-16
申请人： DSM IP Assets B.V. , SAGT, Cornelis, Maria, Jacobus , PEIJ, VAN, Noël Nicolaas Maria Elisabeth , LANGE, DE, Linda , BEISHUIZEN, Martina , DONKERS, Serge, Petrus
发明人： SAGT, Cornelis, Maria, Jacobus , PEIJ, VAN, Noël Nicolaas Maria Elisabeth , LANGE, DE, Linda , BEISHUIZEN, Martina , DONKERS, Serge, Petrus
IPC分类号： C07K14/14
CPC分类号： C07K14/395
摘要： The present invention relates to polypeptides that have an activity corresponding to at least one activity of the SEC61 polypeptide, polynucleotides encoding these polypeptides and the use thereof in the preparation of host cells suitable for production of a polypeptide of interest. Such host cells may have an increased capacity to secrete a polypeptide of interest.
摘要翻译：本发明涉及具有对应于SEC61多肽的至少一种活性的活性的多肽，编码这些多肽的多核苷酸及其在制备适合于产生感兴趣多肽的宿主细胞中的用途。这样的宿主细胞可能具有增加的分泌感兴趣的多肽的能力。

10. 发明申请

WO2012001169A1 A METHOD FOR THE PRODUCTION OF A COMPOUND OF INTEREST 审中-公开
标题翻译：一种生产化合物的方法
公开(公告)号：WO2012001169A1
公开(公告)日：2012-01-05
申请号：PCT/EP2011/061163
申请日：2011-07-01
申请人： DSM IP ASSETS B.V. , PEIJ, VAN, Noël Nicolaas Maria Elisabeth , HANS, Marcus , BEISHUIZEN, Martina , SCHIPPER, Dick , HOEVEN, VAN DER, Robertus Antonius Mijndert , SCHOUTEN, Olaf Leonardus
发明人： PEIJ, VAN, Noël Nicolaas Maria Elisabeth , HANS, Marcus , BEISHUIZEN, Martina , SCHIPPER, Dick , HOEVEN, VAN DER, Robertus Antonius Mijndert , SCHOUTEN, Olaf Leonardus
IPC分类号： C12N15/80 , C12N9/00 , C12N1/14
CPC分类号： C12P21/02 , C12N9/18 , C12N9/93 , C12N15/80 , C12P21/00
摘要： The present invention relates to a method for the production of a compound of interest by microbial fermentation, wherein the microbial host cell used has been modified in its genome such that it results in a deficiency in the production of at least one non-ribosomal peptide synthase. The present invention further relates to a microbial host cell that has been modified in its genome such that it results in a deficiency in the production of at least one non-ribosomal peptide synthase. The invention further relates to a compound of interest.
摘要翻译：本发明涉及通过微生物发酵生产感兴趣的化合物的方法，其中使用的微生物宿主细胞在其基因组中已被修饰，从而导致至少一种非核糖体肽合成酶的产生缺陷。本发明还涉及在其基因组中已被修饰的微生物宿主细胞，从而导致至少一种非核糖体肽合成酶的产生缺陷。本发明还涉及目的化合物。

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