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11. 发明申请

WO2010015625A1 ADIPOYL-7-ADCA PRODUCING STRAINS 审中-公开
标题翻译： ADIPOYL-7-ADCA生产菌株
公开(公告)号：WO2010015625A1
公开(公告)日：2010-02-11
申请号：PCT/EP2009/060088
申请日：2009-08-04
申请人： DSM IP ASSETS B.V. , VAN DEN BERG, Marco, Alexander , BOVENBERG, Roelof, Ary, Lans
发明人： VAN DEN BERG, Marco, Alexander , BOVENBERG, Roelof, Ary, Lans
IPC分类号： C12N1/14 , C12N15/01
CPC分类号： C12P37/00 , C12N9/0006 , C12N9/001 , C12N9/1029 , C12N9/88 , C12N9/93
摘要： The present invention relates to a mutant microbial strain capable of producing an N-adipoylated β-lactam compound when cultured in a culture medium comprising adipic acid characterized in that the strain has an improved incorporation yield of the adipic acid from the culture medium into the N-adipoylated β-lactam compound compared to the non-mutant parent strain.
摘要翻译：本发明涉及在含有己二酸的培养基中培养时能够产生N-己二酰化的β-内酰胺化合物的突变微生物菌株，其特征在于该菌株具有改进的己二酸与非突变亲本菌株相比，从培养基中转化成N-己二酰化β-内酰胺化合物。

12. 发明申请

WO2008040731A2 PRODUCTION OF BETA-LACTAM ANTIBIOTICS 审中-公开
标题翻译： β-内酰胺抗生素的生产
公开(公告)号：WO2008040731A2
公开(公告)日：2008-04-10
申请号：PCT/EP2007/060460
申请日：2007-10-02
申请人： DSM IP ASSETS B.V. , BOER, Rémon , HANS, Marcus , BOVENBERG, Roelof, Ary, Lans , KLAASSEN, Paul , LAAN, VAN DER, Jan Metske
发明人： HANS, Marcus , BOVENBERG, Roelof, Ary, Lans , KLAASSEN, Paul , LAAN, VAN DER, Jan Metske
IPC分类号： C12N9/02 , C12P37/00
CPC分类号： C12N9/0004
摘要： The present invention describes a process for the production of an N-α-amino-hydroxyphenylacetyl or an N-α-aminophenylacetyl β-lactam antibiotic comprising an IPNS-catalysed conversion of a precursor tripeptide hydroxyphenylglycyl-cysteinyl- valine (HpgCV) or phenylglycyl-cysteinyl-valine (PgCV), respectively, to the N- hydroxyphenylglycyl or the N-phenylglycyl β-lactam antibiotic, respectively. The tripeptide HpgCV or the tripeptide PgCV may further be prepared by contacting the amino acids hydroxyphenylglycine (Hpg) or phenylglycine (Pg), cystein (C) and valine (V) with a non-ribosomal peptide synthetase (NRPS) to effect formation of the tripeptide HpgCV or the tripeptide PgCV, the NRPS comprising a first module M1 specific for Hpg or Pg, a second module M2 specific for C and a third module M3 specific for V. An IPNS is further provided having an improved activity in this conversion, as well as an NRPS catalysing the formation of the tripeptides. Also a host cell is provided capable of fermentatively producing β-lactam antibiotics with N-α-amino-hydroxyphenylacetyl or an N-α-aminophenylacetyl side chains.
摘要翻译：本发明描述了用于生产N-α-氨基 - 羟基苯基乙酰基或N-α-氨基苯基乙酰基β-内酰胺抗生素的方法，其包含IPNS-催化的前体三肽羟基苯基甘氨酰 - 半胱氨酰 - 缬氨酸（HpgCV）或苯基甘氨酰 - 半胱氨酰 - 缬氨酸（PgCV）分别与N-羟基苯基甘氨酰基或N-苯基甘氨酰基β-内酰胺抗生素接触。三肽HpgCV或三肽PgCV还可以通过使氨基酸羟苯甘氨酸（Hpg）或苯基甘氨酸（Pg），半胱氨酸（C）和缬氨酸（V）与非核糖体肽合成酶（NRPS）接触以制备三肽HpgCV或三肽PgCV，NRPS包含特异于Hpg或Pg的第一模块M1，特异于C的第二模块M2和特异于V的第三模块M3。进一步提供具有改进的活性的IPNS，以及催化三肽形成的NRPS。还提供了能够用N-α-氨基 - 羟基苯基乙酰基或N-α-氨基苯基乙酰基侧链发酵产生β-内酰胺抗生素的宿主细胞。

13. 发明申请

WO2010015624A1 ADIPOYL-7-ADCA PRODUCING STRAINS 审中-公开
标题翻译： ADIPOYL-7-ADCA生产菌株
公开(公告)号：WO2010015624A1
公开(公告)日：2010-02-11
申请号：PCT/EP2009/060086
申请日：2009-08-04
申请人： DSM IP ASSETS B.V. , KOEKMAN, Bertus, Pieter , BERG, VAN DEN, Marco, Alexander , BOVENBERG, Roelof, Ary, Lans
发明人： KOEKMAN, Bertus, Pieter , BERG, VAN DEN, Marco, Alexander , BOVENBERG, Roelof, Ary, Lans
IPC分类号： C12N1/14
CPC分类号： C12N15/01 , C12N1/14 , C12P37/00
摘要： The present invention relates to a mutant microbial strain capable of producing an N-adipoylated β-lactam compound when cultured in a culture medium comprising adipic acid characterized in that the strain has an improved incorporation yield of the adipic acid from the culture medium into the N-adipoylated β-lactam compound compared to the non-mutant parent strain.
摘要翻译：本发明涉及在包含己二酸的培养基中培养时能够产生N-己二酰化的β-内酰胺化合物的突变型微生物菌株，其特征在于该菌株具有改善的己二酸从培养基到N 邻苯二甲酰化的β-内酰胺化合物与非突变亲本菌株相比。

14. 发明申请

WO2007122249A1 PRODUCTION OF COMPOUNDS IN A RECOMBINANT HOST 审中-公开
标题翻译：在重组生物中生产化合物
公开(公告)号：WO2007122249A1
公开(公告)日：2007-11-01
申请号：PCT/EP2007/054045
申请日：2007-04-25
申请人： DSM IP Assets B.V. , BOVENBERG, Roelof, Ary, Lans , VAN DEN BERG, Marco Alexander , HAGE, Suzanne , KLAASSEN, Paul , MEIJRINK, Bernard , RAAMSDONK, Lourina, Madeleine
发明人： BOVENBERG, Roelof, Ary, Lans , VAN DEN BERG, Marco Alexander , HAGE, Suzanne , KLAASSEN, Paul , MEIJRINK, Bernard , RAAMSDONK, Lourina, Madeleine
IPC分类号： C07K14/385 , C12N1/16
CPC分类号： C12N9/1029 , C12N9/0004 , C12N9/93 , C12P7/02 , C12P13/02 , C12P17/06 , C12P17/181 , C12P17/182 , C12P17/188
摘要： The present invention provides a recombinant Penicillium chrysogenum strain characterized in that a gene selected from the list consisting of penDE, pcbAB and pcbC is inactivated and the use of such a strain for the preparation of a compound of interest. Furthermore, it is an object of the present invention to provide a method for the production of a compound of interest in a eukaryotic recombinant microorganism comprising the steps of : (a) Reducing the level of secondary metabolite production in said microorganism with 50-100%; (b) Introducing a heterologous gene into said microorganism
摘要翻译：本发明提供重组产黄青霉菌株，其特征在于，从PenDE，pcbAB和pcbC列表中选出的基因被灭活，并且使用这样的菌株来制备感兴趣的化合物。此外，本发明的目的是提供一种在真核重组微生物中生产感兴趣的化合物的方法，包括以下步骤：（a）降低所述微生物中次级代谢产物的产生水平，其中50-100％ ; （b）将异源基因引入所述微生物

15. 发明申请

WO2006089946A3 ALTERED ISOPENICILLIN-N ACYLTRANSFERASE POLYPEPTIDES AND RELATED POLYNUCLEOTIDES 审中-公开
公开(公告)号：WO2006089946A3
公开(公告)日：2006-08-31
申请号：PCT/EP2006/060256
申请日：2006-02-24
申请人： DSM IP Assets B.V. , BOVENBERG, Roelof, Ary, Lans , KREBBER, Anke , COX, Anthony , TO LA CHING, Charlene , TOBIN, Matthew , JENNE, Stephane J. , CHEN, Yong Hong
发明人： BOVENBERG, Roelof, Ary, Lans , KREBBER, Anke , COX, Anthony , TO LA CHING, Charlene , TOBIN, Matthew , JENNE, Stephane J. , CHEN, Yong Hong
IPC分类号： C12N9/10 , C12N15/54 , C12N1/21 , C12P37/00
摘要： The present invention relates to novel acyltransferase polypeptides, as well as the polynucleotides that encode them, that are particularly useful in the production of beta-lactam intermediates and antibiotic compounds having adipoyl side chains. The present invention is also directed to related vectors, host cells, and methods for making and using the novel acyltransferase polypeptides.

16. 发明申请

WO2006061425A2 PRODUCTION OF ß-LACTAMS IN SINGLE CELLS 审中-公开
标题翻译：在单细胞中生产β-LACTAMS
公开(公告)号：WO2006061425A2
公开(公告)日：2006-06-15
申请号：PCT/EP2005/056619
申请日：2005-12-08
申请人： DSM IP Assets B.V. , BERG, VAN DEN, Marco Alexander , BOVENBERG, Roelof, Ary, Lans , NOORMAN, Hendrik, Jan , ROMEIN, Bastiaan
发明人： BERG, VAN DEN, Marco Alexander , BOVENBERG, Roelof, Ary, Lans , NOORMAN, Hendrik, Jan , ROMEIN, Bastiaan
IPC分类号： C12N15/09 , C12P17/18 , C12P37/00 , C12P35/00 , G01N33/50
CPC分类号： C12P37/00 , C12P17/184 , C12P35/00
摘要： The present invention describes the transformation of a microorganism that does not naturally produce a β-lactam compound with polynucleotides involved in the biosynthesis of β-lactam compounds and the use of such transformed microorganisms in the production of β-lactam compounds or in the identification of genes or factors involved in the synthesis of a β-lactam compound.
摘要翻译：本发明描述了不参与β-内酰胺化合物生物合成的多核苷酸天然产生β-内酰胺化合物的微生物的转化，以及这些转化的微生物在生产β-内酰胺化合物中的用途或鉴定参与合成β-内酰胺化合物的基因或因子。

17. 发明申请

WO2004106347A1 CEPHEM COMPOUND 审中-公开
标题翻译： CEPHEM化合物
公开(公告)号：WO2004106347A1
公开(公告)日：2004-12-09
申请号：PCT/NL2004/000367
申请日：2004-05-24
申请人： DSM IP ASSETS B.V. , VAN DEN BERG, Marco, Alexander , BOVENBERG, Roelof, Ary, Lans , RAAMSDONK, Lourina, Madeleine, Leonie , SUTHERLAND, John, David , DE VROOM, Erik , VOLLINGA, Roeland, Christiaan, Roel
发明人： VAN DEN BERG, Marco, Alexander , BOVENBERG, Roelof, Ary, Lans , RAAMSDONK, Lourina, Madeleine, Leonie , SUTHERLAND, John, David , DE VROOM, Erik , VOLLINGA, Roeland, Christiaan, Roel
IPC分类号： C07D501/00
CPC分类号： C07D501/00
摘要： The present invention is concerned with a novel cephem compound, with a process for the production of this compound, which process may contain or consist of fermentative steps, chemical steps, and/or biotransformation steps. A cephem compound according to the present invention characterised by formula (I) or a salt or ester thereof, wherein R is selected from the group consisting of (carboxymethylthio)propionyl (carboxyethylthio)propionyl Y- CH2-CO15 wherein Y is phenyl, phenoxy or tetrazolyl HOOC-X-CO wherein X is defined as (CH 2 ) 4 or wherein X is defined as (CH 2 )P-A-(CH 2 )q, wherein p and q each individually are 0, 1, 2, 3 or 4, and A is CH=CH, C-=C, CHB, C=O, O, S, NH, the nitrogen optionally being substituted or the sulfur optionally being oxidized, and B is hydrogen, halogen, C 1-3 alkoxy, hydroxyl, or optionally substituted methyl, with the proviso that p+q should be 2 or 3, when A is CH=CH or C=-C, or p+q should be 3 or 4, when A is CHB, C=O, 0, S or NH or wherein X is (CH 2 ) m -CH=A-(CH2) n or (CH 2 ) m -C=-C-(CH 2 ) n , wherein m and n each individually are 0, 1, 2 or 3 and m+n = 2 or 3, and A is CH or N, or wherein X is (CH2)p-CH=CH-C H=C-(CH2)q wherein p and q each individually are 0 or 1 and p+q = 0 or 1 and wherein R' is selected from the group consisting of OH O-(alkyl 1-6C) wherein the alkyl can be straight or branched and O-C(alkyl 1-6C)-O-(alkyl 1-6C) wherein the alkyl groups can be straight or branched can inter alia be prepared by fermentative techniques according to the invention and in particular using a suitable microorganism possessing or being transformed with the genes needed for conversion of an appropriate acyl-6-aminopenicillanic acid into the desired compound.
摘要翻译：本发明涉及一种新的头孢烯化合物，其具有生产该化合物的方法，该方法可以含有或由发酵步骤，化学步骤和/或生物转化步骤组成。根据本发明的头孢烯化合物，其特征在于式（I）化合物或其盐或酯，其中R选自（羧甲硫基）丙酰基（羧乙硫基）丙酰基Y-CH 2 -CO 15，其中Y是苯基，苯氧基或四唑基HOOC-X-CO，其中X定义为（CH 2）4或其中X定义为（CH 2）PA-（CH 2）q，其中p和q各自独立地为0,1,2,3或4，并且A 是CH = CH，C = C，CHB，C = O，O，S，NH，任选被取代的氮或任选被氧化的硫，B是氢，卤素，C 1-3烷氧基，羟基或任选地取代的甲基，条件是当A为CH = CH或C = -C时，p + q应为2或3，或p + q应为3或4，当A为CHB时，C = O，O，S 或NH或其中X是（CH 2）m -CH = A-（CH 2）n或（CH 2）m C = -C-（CH 2）n，其中m和n各自独立地是0,1,2或3和m + n = 2或3，A为CH或N，或其中X为（CH 2）p -CH = CH-C H = C-（CH 2）q，其中p和q各自各自为0或1，p + q = 0或1和其中R'选自OH -O-（烷基1-6C），其中烷基可以是直链或支链和OC（烷基1-6C）-O-（烷基1-6C），其中烷基可以是直链或支链可以特别通过根据本发明的发酵技术制备，特别是使用具有或正在转化合适的酰基-6-氨基青霉烷酸所需基因的合适微生物进入所需化合物。

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