公开(公告)号：WO2012150861A1

公开(公告)日：2012-11-08

申请号：PCT/NL2012/050284

申请日：2012-04-26

申请人： STICHTING TOP INSTITUTE FOOD AND NUTRITION ,  VAN BOKHORST-VAN DE VEEN, Hermien ,  LEE,, I-Chiao ,  WELS, Michiel Wouter Wilhelmus ,  DE VOS, Paulus ,  BRON, Peter Allard ,  BONGERS, Roger Samuel ,  WIERSMA, Anne ,  KLEEREBEZEM, Michiel

发明人： VAN BOKHORST-VAN DE VEEN, Hermien ,  LEE,, I-Chiao ,  WELS, Michiel Wouter Wilhelmus ,  DE VOS, Paulus ,  BRON, Peter Allard ,  BONGERS, Roger Samuel ,  WIERSMA, Anne ,  KLEEREBEZEM, Michiel

IPC分类号： C12N1/21 ,  C07K14/335 ,  A23L1/03 ,  A23L1/30

CPC分类号： A23L1/3014 ,  A23L29/065 ,  A23L33/135 ,  C07K14/335 ,  C12N1/20

摘要： The present invention relates to a method for screening for a bacterium exhibiting enhanced survival properties in the gastro-intestinal tract. The present invention further relates to a method for screening for culture conditions that provide a bacterium exhibiting enhanced survival properties in the gastro-intestinal tract. The present invention further relates to a method for modulating the expression of certain polynucleotides. The present invention further relates to a method for the preparation of a bacterium exhibiting enhanced survival properties in the gastro-intestinal tract. The present invention further relates to a bacterium exhibiting enhanced survival properties in the gastro-intestinal tract. The present invention further relates to a method for the preparation of a food composition. The present invention further relates to a food composition. The present invention further relates to the use of certain polynucleotides in the screening for a bacterium exhibiting enhanced survival properties in the gastro- intestinal tract and/or the screening for culture conditions that provide a bacterium exhibiting enhanced survival properties in the gastro-intestinal tract and/or for the control of culture conditions providing a bacterium exhibiting enhanced survival properties in the gastro-intestinal tract. The present invention further relates to a method for controlling culture conditions providing a bacterium exhibiting enhanced survival properties in the gastro-intestinal tract.

摘要翻译： 本发明涉及筛选在胃肠道中表现出增强的存活性的细菌的方法。 本发明还涉及一种用于筛选提供在胃肠道中表现出增强的存活性的细菌的培养条件的方法。 本发明还涉及调节某些多核苷酸表达的方法。 本发明还涉及一种制备在胃肠道中表现出增强的存活性的细菌的方法。 本发明还涉及在胃肠道中表现出增强的存活性的细菌。 本发明还涉及一种食品组合物的制备方法。 本发明还涉及食品组合物。 本发明还涉及某些多核苷酸在筛选在胃肠道中表现出增强的存活性的细菌和/或筛选提供在胃肠道中表现出增强的存活性的细菌的培养条件下的某些多核苷酸的用途，以及 或用于控制提供在胃肠道中表现出增强的存活性的细菌的培养条件。 本发明还涉及一种控制培养条件的方法，所述培养条件提供在胃肠道中表现出增强的存活性的细菌。

公开(公告)号：WO2006065137A2

公开(公告)日：2006-06-22

申请号：PCT/NL2005/050079

申请日：2005-12-16

申请人： STICHTING TECHNOLOGISCH TOP-INSTITUUT VOEDSELWETENSCHAPPEN ,  NIEROP GROOT, Masja Nathalie ,  DE VOS, Willem Meindert ,  KLEEREBEZEM, Michiel

发明人： NIEROP GROOT, Masja Nathalie ,  DE VOS, Willem Meindert ,  KLEEREBEZEM, Michiel

CPC分类号： C07K14/3156 ,  A61K39/00 ,  A61K39/02 ,  A61K39/07 ,  A61K39/085 ,  A61K39/09 ,  A61K39/092 ,  A61K2039/523

摘要： The current invention provides methods and means for heterologous expression, production and/or secretion of complex capsular polysaccharides in non- pathogenic, non-invasive Gram-positive bacteria. The invention in particular provides non- pathogenic, non- invasive Gram-positive bacteria capable of expression and/or secretion of heterologous, complex polysaccharides from a pathogenic bacterial species. Such bacteria and polysaccharides produced therein may be applied according to the invention to provide compositions for vaccination for the treatment and prevention of infectious bacterial diseases.

摘要翻译： 本发明提供用于在非致病性非侵入性革兰氏阳性细菌中异源表达，生产和/或分泌复合荚膜多糖的方法和手段。 本发明特别提供了能够表达和/或分泌来自致病细菌物种的异源复合多糖的非致病性非侵袭性革兰氏阳性细菌。 其中产生的这些细菌和多糖可根据本发明应用以提供用于接种治疗和预防感染性细菌疾病的组合物。

公开(公告)号：WO2005040387A1

公开(公告)日：2005-05-06

申请号：PCT/NL2003/000733

申请日：2003-10-28

申请人： FRIESLAND BRANDS B.V. ,  BRON, Peter, Allard ,  DE VOS, Willem, Meindert ,  KLEEREBEZEM, Michiel

发明人： BRON, Peter, Allard ,  DE VOS, Willem, Meindert ,  KLEEREBEZEM, Michiel

IPC分类号： C12N15/74

CPC分类号： A61K48/0058 ,  A61K48/00 ,  A61K48/0075 ,  A61K2035/11 ,  C12N15/746

摘要： The present invention relates to the site-specific production of biologically active substances by recombinant micro-organisms in body cavities of a human or animal subject. The invention provides transcription regulatory sequences, which are specifically induced in the gastrointestinal tract (GI-tract) of subjects and methods for their use for in vivo site-specific expression of nucleic acid sequences encoding biologically active substances.

摘要翻译： 本发明涉及通过重组微生物在人或动物受试者的体腔中的生物活性物质的位点特异性生产。 本发明提供在受试者的胃肠道（GI道）中特异性诱导的转录调节序列及其用于体内位点特异性表达编码生物活性物质的核酸序列的方法。

公开(公告)号：WO03076463A8

公开(公告)日：2004-10-07

申请号：PCT/NL0300178

申请日：2003-03-11

申请人： WAGENINGEN CT FOR FOOD SCIENCE ,  KARATZAS KIMON ANDREAS ,  BENNIK MARIA HENRICA JACOBA ,  ABEE TJAKKO ,  KLEEREBEZEM MICHIEL ,  DE VOS WILLEM MEINDERT

发明人： KARATZAS KIMON ANDREAS ,  BENNIK MARIA HENRICA JACOBA ,  ABEE TJAKKO ,  KLEEREBEZEM MICHIEL ,  DE VOS WILLEM MEINDERT

IPC分类号： C07K14/195 ,  C07K14/32 ,  C07K14/335 ,  C12N1/21 ,  C12N15/31 ,  A61K35/74 ,  A61K39/02 ,  C12P1/04

CPC分类号： A61K35/747 ,  A61K2039/522 ,  C07K14/195 ,  C07K14/32 ,  C07K14/335

摘要： The present invention relates to Gram positive bacteria with increased stress tolerance, reduced virulence, and/or reduced mobility, as a result of an altered CtsR protein. The alteration of the CtsR protein in particular concerns an alteration of the conserved glycine-rich region in the CtsR protein. The invention further relates to nucleic acid encoding the altered CtsR proteins. The altered Gram positive bacteria may be used in fermentation processes and may be used as delivery vehicles for site specific delivery of therapeutic proteins such as vaccines.

摘要翻译： 本发明涉及由于改变的CtsR蛋白而具有增加的胁迫耐受性，降低的毒力和/或降低的迁移率的革兰氏阳性细菌。 CtsR蛋白的改变特别涉及CtsR蛋白中保守的富含甘氨酸的区域的改变。 本发明还涉及编码改变的CtsR蛋白的核酸。 改变的革兰氏阳性细菌可用于发酵过程中，并且可以用作用于特异性递送治疗性蛋白质例如疫苗的递送载体。

公开(公告)号：WO2004013332A1

公开(公告)日：2004-02-12

申请号：PCT/NL2003/000555

申请日：2003-08-01

申请人： NEDERLANDS INSTITUUT VOOR ZUIVELONDERZOEK ,  NOORDMAN, Herman, Wouter ,  HUGENHOLTZ, Jeroen ,  KLEEREBEZEM, Michiel

发明人： NOORDMAN, Herman, Wouter ,  HUGENHOLTZ, Jeroen ,  KLEEREBEZEM, Michiel

IPC分类号： C12N15/53

CPC分类号： C12N9/0073 ,  C12N9/0006 ,  C12N9/0077 ,  C12P7/18 ,  C12P7/22 ,  C12P7/26 ,  C12P7/42 ,  C12P7/62 ,  C12P17/08 ,  C12R1/225

摘要： The present invention relates to a method for converting a carbon-containing substrate of an NAD(P)H-dependent enzyme. A lactic acid bacterium which expresses the NAD(P)H dependent enzyme is used for the conversion. In this way more than 90 % of a substrate may be converted.

摘要翻译： 本发明涉及一种NAD（P）H依赖性酶转化含碳底物的方法。 用于表达NAD（P）H依赖性酶的乳酸菌用于转化。 以这种方式，可以转化90％以上的底物。

公开(公告)号：WO9936556A3

公开(公告)日：1999-10-14

申请号：PCT/NL9900021

申请日：1999-01-15

申请人： NL ZUIVELONDERZOEK INST ,  HOLS PASCAL ,  KLEEREBEZEM MICHIEL ,  KUIPERS OSCAR PAUL ,  FERAIN THIERRY ,  DELCOUR JEAN MARCELIN ALAIN MA ,  VOS WILLEM MEINDERT DE

发明人： HOLS PASCAL ,  KLEEREBEZEM MICHIEL ,  KUIPERS OSCAR PAUL ,  FERAIN THIERRY ,  DELCOUR JEAN MARCELIN ALAIN MA ,  DE VOS WILLEM MEINDERT

IPC分类号： A23C19/032 ,  C12N1/21 ,  C12N9/06 ,  C12N15/09 ,  C12P13/06 ,  C12R1/01 ,  C12R1/225 ,  C12N15/74

CPC分类号： C12P13/06

摘要： The present invention relates to a process for preparing alanine, especially L-alanine, by culturing a genetically modified microorganism that is able to produce alanine from glucose, characterized in that the microorganism used is one whose native sugar metabolism has been diverted to alanine formation, especially L-alanine formation, in such a manner that essentially more than 40 %, preferably more than 60 % and more preferably more than 75 % of the carbon consumed from the medium is converted into alanine, especially via pyruvate. The microorganism is preferably a homofermentative microorganism, especially a lactic acid bacterium, more particularly (a strain of) L. lactis, and is preferably a food-grade microorganism. The invention can be used for both the in situ and the stereospecific preparation of alanine. The invention also relates to the microorganisms and recombinant DNA molecules that can be used in the invention and to the alanine and alanine-containing (food) products obtained according to the invention.

摘要翻译： 本发明涉及通过培养能够从葡萄糖生产丙氨酸的遗传修饰的微生物来制备丙氨酸，特别是L-丙氨酸的方法，其特征在于使用的微生物是将天然糖代谢转移到丙氨酸形成的微生物， 特别是L-丙氨酸形成，使得从培养基中消耗的碳的基本上超过40％，优选大于60％，更优选大于75％被转化为丙氨酸，特别是通过丙酮酸盐。 微生物优选是均匀发酵微生物，特别是乳酸菌，更特别是（乳酸乳杆菌）菌株，优选食品级微生物。 本发明可用于丙氨酸的原位和立体特异性制备。 本发明还涉及可用于本发明的微生物和重组DNA分子以及根据本发明获得的含丙氨酸和丙氨酸（食品）产品。

公开(公告)号：WO2008079009A1

公开(公告)日：2008-07-03

申请号：PCT/NL2007/050694

申请日：2007-12-21

申请人： Campina Nederland Holding B.V. ,  ZUURENDONK, Peter Frederik ,  KLEEREBEZEM, Michiel ,  SNEL, Johannes ,  MARCO, Maria ,  SAVELKOUL, Hubertus Franciscus Jozef

发明人： ZUURENDONK, Peter Frederik ,  KLEEREBEZEM, Michiel ,  SNEL, Johannes ,  MARCO, Maria ,  SAVELKOUL, Hubertus Franciscus Jozef

IPC分类号： A23L1/30 ,  C12N1/20 ,  C12R1/225 ,  C12R1/25

CPC分类号： C12R1/225 ,  A23C9/1234 ,  A23C15/123 ,  A23C19/0323 ,  A23L33/135 ,  A23V2002/00 ,  A23Y2220/67 ,  A61K35/747 ,  C12N1/20 ,  C12R1/25 ,  A23V2200/304 ,  A23V2200/3204

摘要： The present invention relates to immuno modulat ing probiotic lactic acid bacteria, to methods wherein the bacteria are used to reduce allergy, and to food products wherein the bacteria may be in incorporated to reduce allergy upon consumption of the product. Preferred probiotic lactic acid bacteria stimulate the Th1 and/or Th3 responses and/or represses Th2 responses as may be determined by the cytokine profiles that are induced in human peripheral blood mononuclear cells upon coincubation with the lactic acid bacteria.

摘要翻译： 本发明涉及免疫调节益生菌乳酸菌，其中使用细菌来减少过敏的方法，以及其中可以并入细菌以减少产品消费过敏的食品。 优选的益生菌乳酸细菌刺激Th1和/或Th3应答和/或镇压Th2应答，如通过与乳酸菌共调节时在人外周血单核细胞中诱导的细胞因子谱所确定的。

公开(公告)号：WO2003076463A2

公开(公告)日：2003-09-18

申请号：PCT/NL2003/000178

申请日：2003-03-11

申请人： WAGENINGEN CENTRE FOR FOOD SCIENCES ,  KARATZAS, Kimon, Andreas ,  BENNIK, Maria, Henrica, Jacoba ,  ABEE, Tjakko ,  KLEEREBEZEM, Michiel ,  DE VOS, Willem, Meindert

发明人： KARATZAS, Kimon, Andreas ,  BENNIK, Maria, Henrica, Jacoba ,  ABEE, Tjakko ,  KLEEREBEZEM, Michiel ,  DE VOS, Willem, Meindert

IPC分类号： C07K14/195

CPC分类号： A61K35/747 ,  A61K2039/522 ,  C07K14/195 ,  C07K14/32 ,  C07K14/335

摘要： The present invention relates to Gram positive bacteria with increased stress tolerance, reduced virulence, and/or reduced mobility, as a result of an altered CtsR protein. The alteration of the CtsR protein in particular concerns an alteration of the conserved glycine-rich region in the CtsR protein. The invention further relates to nucleic acid encoding the altered CtsR proteins. The altered Gram positive bacteria may be used in fermentation processes and may be used as delivery vehicles for site specific delivery of therapeutic proteins such as vaccines.

摘要翻译： 本发明涉及由于改变的CtsR蛋白而具有增加的胁迫耐受性，降低的毒力和/或降低的迁移率的革兰氏阳性细菌。 CtsR蛋白的改变特别涉及CtsR蛋白中保守的富含甘氨酸的区域的改变。 本发明还涉及编码改变的CtsR蛋白的核酸。 改变的革兰氏阳性细菌可用于发酵过程中，并且可以用作用于特异性递送治疗性蛋白质例如疫苗的递送载体。

公开(公告)号：WO2011071370A1

公开(公告)日：2011-06-16

申请号：PCT/NL2010/050647

申请日：2010-10-05

申请人： CAMPINA NEDERLAND HOLDING B.V. ,  SNEL, Johannes ,  KLEEREBEZEM, Michiel ,  ZWIJSEN, Renate Maria Louise ,  SMIT, Bart ,  NOORDMAN, Wouter Herman

发明人： SNEL, Johannes ,  KLEEREBEZEM, Michiel ,  ZWIJSEN, Renate Maria Louise ,  SMIT, Bart ,  NOORDMAN, Wouter Herman

IPC分类号： A61K35/74 ,  C12N1/20

CPC分类号： A61K35/74 ,  C12N1/20

摘要： The present invention relates to immunomodulating probiotic lactic acid bacteria, to methods wherein the bacteria are used to reduce allergy, and to food products wherein the bacteria may be in incorporated to reduce allergy upon consumption of the product. Preferred probiotic lactic acid bacteria stimulate the Th1 and/or Th3 responses and/or represses Th2 responses in vivo asmay be determined by the cytokine profiles that are induced in humans upon consumption of the lactic acid bacteria.

摘要翻译： 本发明涉及免疫调节益生菌乳酸菌，其中细菌用于减少过敏的方法，以及其中可以并入细菌以减少产品消费过敏的食品。 优选的益生菌乳酸菌刺激Th1和/或Th3应答和/或抑制体内Th2应答，可以通过在消耗乳酸菌时在人体中诱导的细胞因子谱来确定。

公开(公告)号：WO2009035330A1

公开(公告)日：2009-03-19

申请号：PCT/NL2008/050600

申请日：2008-09-12

申请人： STICHTING TOP INSTITUTE FOOD AND NUTRITION ,  KONSTANTINOV, Sergey Rumenov ,  LAMBERT, Jolanda ,  VAN DER MEER - VAN KRAAIJ, Cindy Mathilda ,  DE VOS, Willem Meindert ,  KLEEREBEZEM, Michiel

发明人： KONSTANTINOV, Sergey Rumenov ,  LAMBERT, Jolanda ,  VAN DER MEER - VAN KRAAIJ, Cindy Mathilda ,  DE VOS, Willem Meindert ,  KLEEREBEZEM, Michiel

IPC分类号： C07K14/335 ,  A61K35/74

CPC分类号： C07K14/335 ,  A61K38/00

摘要： The invention relates to a polypeptide which is able to interact with a DC-SIGN and to a host cell overexpressing this polypetide. Such polypeptide and/or encoding nucleic acid molecule and/or corresponding nucleic acid construct and/or sai d host cell are used as medicament, preferably for preventing or treating inflammatory gastrointestinal tract disease and/or inducing tolerance.

摘要翻译： 本发明涉及能够与DC-SIGN和过表达该多肽的宿主细胞相互作用的多肽。 此类多肽和/或编码核酸分子和/或相应的核酸构建体和/或宿主细胞用作药物，优选用于预防或治疗炎症性胃肠道疾病和/或诱导耐受性。