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1. 发明授权

US5747285A DNA comprising regulatory regions from gene y of penicillium chrysogenum 失效
标题翻译： DNA包含来自产黄青霉的基因y的调节区
公开(公告)号：US5747285A
公开(公告)日：1998-05-05
申请号：US207900
申请日：1994-03-08
申请人： Roelof Ary Lans Bovenberg , Adrianus Wilhelmus Hermanus Vollebregt , Pieter Van Solingen
发明人： Roelof Ary Lans Bovenberg , Adrianus Wilhelmus Hermanus Vollebregt , Pieter Van Solingen
IPC分类号： C07K14/37 , C07K14/375 , C12N9/10 , C12N9/16 , C12N9/88 , C12N15/10 , C12N15/52 , C12N15/80 , C12P37/00 , C12N15/62
CPC分类号： C12N15/52 , C07K14/37 , C07K14/375 , C12N15/1034 , C12N15/80 , C12N9/1029 , C12N9/16 , C12N9/88 , C12P37/00 , C07K2319/00 , C07K2319/02
摘要： A gene expression system and a protein secretion system for eukaryotic, especially fungal, microorganisms has been provided for.
摘要翻译：已经提供了用于真核的，特别是真菌的微生物的基因表达系统和蛋白质分泌系统。

2. 发明授权

US06518039B2 Process for the fermentative production of deacylated cephalosporins 失效
标题翻译：脱酰头孢菌素发酵生产工艺
公开(公告)号：US06518039B2
公开(公告)日：2003-02-11
申请号：US09202798
申请日：1999-05-17
申请人： Maarten Nieboer , Erik De Vroom , Johannis Lugtenburg , Dirk Schipper , Adrianus Wilhelmus Hermanus Vollebregt , Roelof Ary Lans Bovenberg
发明人： Maarten Nieboer , Erik De Vroom , Johannis Lugtenburg , Dirk Schipper , Adrianus Wilhelmus Hermanus Vollebregt , Roelof Ary Lans Bovenberg
IPC分类号： C12P3504
CPC分类号： C12N9/0071 , C12N9/1029 , C12P35/00 , C12P37/04
摘要： The present invention discloses a process for the production of N-deacylated cephalosporin compounds via the fermentative production of their 7-acylated counterparts.
摘要翻译：本发明公开了通过其7-酰化对应物的发酵生产来生产N-脱酰头孢菌素化合物的方法。

3. 发明授权

US06410259B1 Process for the fermentative production of deacylated cephalosporins 失效
标题翻译：脱酰头孢菌素发酵生产工艺
公开(公告)号：US06410259B1
公开(公告)日：2002-06-25
申请号：US09202797
申请日：1999-08-26
申请人： Maarten Nieboer , Erik De Vroom , Johannis Lugtenburg , Dirk Schipper , Adrianus Wilhelmus Hermanus Vollebregt , Roelof Ary Lans Bovenberg
发明人： Maarten Nieboer , Erik De Vroom , Johannis Lugtenburg , Dirk Schipper , Adrianus Wilhelmus Hermanus Vollebregt , Roelof Ary Lans Bovenberg
IPC分类号： C12P3500
CPC分类号： C12N9/0071 , C12N9/1029 , C12P35/00 , C12P37/04 , Y10S435/935
摘要： The present invention disclosures a process for the production of N-deacylated cephalosporin compounds via the fermentative production of their 7-acylated counterparts.
摘要翻译：本发明公开了通过其7-酰化对应物的发酵生产来生产N-脱酰头孢菌素化合物的方法。

4. 发明授权

US6020151A Process for the production of 7-ADCA via expandase activity on penicillin G 失效
标题翻译：通过青霉素G上的扩增酶活性生产7-ADCA的方法
公开(公告)号：US6020151A
公开(公告)日：2000-02-01
申请号：US973292
申请日：1998-02-18
申请人： Roelof Ary Lans Bovenberg , Bertus Pieter Koekman , Dirk Schipper , Adrianus Wilhelmus Hermanus Vollebregt
发明人： Roelof Ary Lans Bovenberg , Bertus Pieter Koekman , Dirk Schipper , Adrianus Wilhelmus Hermanus Vollebregt
IPC分类号： C12N15/09 , C12N9/02 , C12N15/00 , C12P35/00 , C12R1/365 , C12R1/465 , C12P37/02 , C07D501/00 , C12P35/02
CPC分类号： C12N9/0071 , C12P35/00
摘要： A process is taught for the preparation and recovery of 7-aminodesacetoxycephalosporanic acid (7-ADCA) via enzymatic ring expansion activity on penicillin G, using a Penicillium chrysogenum transformant strain expressing expandase.
摘要翻译： PCT No.PCT / EP96 / 02434 Sec。 371日期1998年2月18日 102（e）1998年2月18日PCT PCT 1996年6月3日PCT公布。出版物WO96 / 38580 日期1996年12月5日教导了使用表达扩环酶的产黄青霉转化株菌株通过青霉素G上的酶环扩展活性制备和回收7-氨基脱乙酸基头孢烷酸（7-ADCA）的方法。

5. 发明申请

US20090233287A1 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：US20090233287A1
公开(公告)日：2009-09-17
申请号：US12298191
申请日：2007-04-25
申请人： Roelof Ary Lans Bovenberg , Marco Alexander Van den Berg , Susanne Hage , Paul Klaassen , Bernard Meijrink , Lourina Madeleine Raamsdonk
发明人： Roelof Ary Lans Bovenberg , Marco Alexander Van den Berg , Susanne Hage , Paul Klaassen , Bernard Meijrink , Lourina Madeleine Raamsdonk
IPC分类号： C12Q1/68 , C12N1/19 , C12P1/00 , C12P17/06 , C12P17/04 , C12P7/02 , C12P17/16 , C12P7/42
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

6. 发明授权

US5919680A Process for the production of SSC's via expandase activity on penicillin G 失效
标题翻译：通过青霉素G的扩增酶活性生产SSC的方法
公开(公告)号：US5919680A
公开(公告)日：1999-07-06
申请号：US757443
申请日：1996-11-27
申请人： John David Sutherland , Roelof Ary Lans Bovenberg , Jan Metske van der Laan
发明人： John David Sutherland , Roelof Ary Lans Bovenberg , Jan Metske van der Laan
IPC分类号： C12N1/21 , C12N9/00 , C12N9/02 , C12N15/52 , C12P35/00 , C12P33/10
CPC分类号： C12N9/0071 , C12P35/00
摘要： An overall process for the preparation and recovery of 7-aminodesacetoxycephalosporanic acid (7-ADCA) via enzymatic ring expansion activity on penicillin G, using a Penicillium chrysogenum transformant strain expressing modified expandase enzyme.
摘要翻译：通过使用表达修饰的扩环酶的产黄青霉转化株菌株通过青霉素G上的酶环扩展活性来制备和回收7-氨基脱乙酸基头孢烷酸（7-ADCA）的整体方法。

7. 发明授权

US5925515A Direct selection of transformants on acetate-containing media 失效
标题翻译：直接选择含有醋酸盐的培养基上的转化体
公开(公告)号：US5925515A
公开(公告)日：1999-07-20
申请号：US861800
申请日：1992-06-11
申请人： Willem Van Hartingsveldt , Robert Franciscus Maria Van Gorcom , R. J. Gouka , Roelof Ary Lans Bovenberg
发明人： Willem Van Hartingsveldt , Robert Franciscus Maria Van Gorcom , R. J. Gouka , Roelof Ary Lans Bovenberg
IPC分类号： C12N9/00 , C12N15/80 , C12Q1/68
CPC分类号： C12N9/93 , C12N15/80
摘要： A transformant selection system has been developed, particularly for a .beta.-lactam producing strain, more particularly for P. chrysogenum, by the complementation of a mutation of said .beta.-lactam producing strain by a homologous selection marker without interfering with .beta.-lactam biosynthesis. Particularly, in applying said transformant selection system a positive selection agent, for instance fluoroacetate is used for the isolation of fac mutants of said strain, particularly of said .beta.-lactam producing strain. Furthermore, a gene entitled facA has been isolated from P. chrysogenum.
摘要翻译： PCT No.PCT / NL91 / 00203 Sec。 371日期：1992年6月11日 102（e）日期1992年6月11日PCT 1991年10月15日PCT PCT。出版物WO92 / 07079 日期1992年4月30日已经开发了转化体选择系统，特别是对于β-内酰胺生产菌株，更特别是产黄青霉菌株，通过同源选择标记物互补所述β-内酰胺生产菌株的突变而不干扰 β-内酰胺生物合成。特别地，在应用所述转化体选择系统中，使用阳性选择剂，例如氟乙酸盐来分离所述菌株，特别是所述β-内酰胺生产菌株的菌种突变体。此外，从产黄青霉中分离出一种名为facA的基因。

8. 发明授权

US5652132A Oxido reductase enzyme system obtainable from P. chrysogenum, the set of genes encoding the same and the use of oxido reductase enzyme systems or genes encoding the same for increasing antibiotic production 失效
标题翻译：从产黄青霉获得的氧化还原酶系统，编码它们的一组基因和使用氧化还原酶系统或编码它们的基因用于增加抗生素生产
公开(公告)号：US5652132A
公开(公告)日：1997-07-29
申请号：US274043
申请日：1994-07-12
申请人： Yair Aharonowitz , Lucia Helena Maria Van Der Voort , Gerald Cohen , Roelof Ary Lans Bovenberg , Rachel Schreiber , Anat Argaman , Yossef Av-Gay , Helena Maria Nan , Alfred Kattevilder , Harriet Pa Lissa , Henk Van Liempt
发明人： Yair Aharonowitz , Lucia Helena Maria Van Der Voort , Gerald Cohen , Roelof Ary Lans Bovenberg , Rachel Schreiber , Anat Argaman , Yossef Av-Gay , Helena Maria Nan , Alfred Kattevilder , Harriet Pa Lissa , Henk Van Liempt
IPC分类号： C12N1/15 , C07K14/00 , C12N9/02 , C12N15/09 , C12N15/53 , C12P35/00 , C12P37/00 , C12R1/82 , C12N9/06
CPC分类号： C12N9/0004 , C07K14/00 , C12N9/0036 , C12P37/00 , Y10S435/935
摘要： A new oxido reductase enzyme activity obtainable from P. chrysogenum, involved in the production of .beta.-lactams, the set of genes encoding said enzyme activity, and a method to enhance said production by using the above-mentioned oxido reductase system and other oxido reductase systems or genes encoding for the same have been disclosed.
摘要翻译：参与β-内酰胺的生产的产黄青素的新的氧化还原酶活性，编码所述酶活性的基因组以及通过使用上述氧化还原酶系统和其它氧化还原酶来增强所述产生的方法已经公开了编码其的系统或基因。

9. 发明申请

US20100009404A1 PRODUCTION OF BETA-LACTAM ANTIBIOTICS 有权
标题翻译：生产β-LACTAM抗生素
公开(公告)号：US20100009404A1
公开(公告)日：2010-01-14
申请号：US12444108
申请日：2007-10-02
申请人： Marcus Hans , Roelof Ary Lans Bovenberg , Paul Klaassen , Rémon Boer , Jan Metske Van Der Laan
发明人： Marcus Hans , Roelof Ary Lans Bovenberg , Paul Klaassen , Rémon Boer , Jan Metske Van Der Laan
IPC分类号： C12P37/00 , C12N9/00 , C12N15/52 , C12N1/21 , C12P35/00
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：本发明描述了制备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，其包括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）分别分别与N-羟基苯基甘氨酰或N-苯基甘氨酰β-内酰胺抗生素。三肽HpgCV或三肽PgCV可以通过使氨基酸羟基苯基甘氨酸（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）接触来进一步制备，以形成三肽HpgCV或三肽PgCV，NRPS包括特定于Hpg或Pg的第一模块M1，特定于C的第二模块M2和特定于V An IPNS的第三模块M3，还具有在该转换中具有改进的活性作为催化三肽形成的NRPS。还提供了能够用N-α-氨基 - 羟基苯基乙酰基或N-α-氨基苯乙酰侧链发酵生产β-内酰胺抗生素的宿主细胞。

10. 发明申请

US20080311631A1 Biosynthetic Production of 4-Amino 4-Deoxychorismate (Adc) and [3R,4R]-4-Amino-3-Hydroxycyclohexa-1,5-Diene-1-Carboxylic Acid (3,4-Cha) 审中-公开
标题翻译： 4-氨基-4-脱氧胸腺嘧啶（Adc）和[3R，4R] -4-氨基-3-羟基环己-1,5-二烯-1-羧酸（3,4-Cha）的生物合成生产
公开(公告)号：US20080311631A1
公开(公告)日：2008-12-18
申请号：US11628459
申请日：2005-06-02
申请人： Marcel Gerhardus Wubbolts , Roelof Ary Lans Bovenberg , Georg Sprenger , Johannes Josef Bongaerts , Stefan Kozak , Michael Muller , Volker Lorbach
发明人： Marcel Gerhardus Wubbolts , Roelof Ary Lans Bovenberg , Georg Sprenger , Johannes Josef Bongaerts , Stefan Kozak , Michael Muller , Volker Lorbach
IPC分类号： C12P13/22 , C12P13/00 , C12N15/63 , C12N1/20 , C07C61/22
CPC分类号： C12P13/04
摘要： The invention relates to a process for the biosynthetic production of 4-amino-4-deoxychorismate (ADC) performed fermentatively in vivo with a 4-amino-4-deoxychorismate synthase, preferably a PabAB bipartite protein (which may be a fusion protein), at an increased level of activity, thereby obtaining a broth comprising ADC and 4-amino-4-deoxyprephenate (ADP), that are recovered. The invention also relates to a further process of converting the ADP into p-aminophenylalanine. The invention, moreover relates to biosynthetic production of [3R,4R]-4-amino-3-hydroxycyclohexa-1,5-diene-1-carboxylic acid (3,4-CHA), by concerted action of such 4-amino-4-deoxychorismate synthase and of an enzyme capable of converting isochorismate into [5S,6S]-5,6 dihydroxycyclohexa-1,3-diene-1-carboxylic acid (2,3-CHD), preferably a phenazine biosynthesis protein PhzD, including recovery of 3,4-CHA. The invention also relates to expression vectors and host cells for use in any of such processes. The invention further relates to the use of 3,4-CHA as a catalytically active product, in particular as a chiral catalyst. And the invention finally relates to synthesis of oseltamivir phosphate from 3,4-CHA.
摘要翻译：本发明涉及用4-氨基-4-脱氧激酶合酶，优选PabAB二分体蛋白（可以是融合蛋白）在体内发酵生物合成生产4-氨基-4-脱氧胸苷酸（ADC）的方法。在增加的活性水平上，从而获得包含ADC和4-氨基-4-脱氧降钙素（ADP）的肉汤，其被回收。本发明还涉及将ADP转化为对氨基苯丙氨酸的另一种方法。本发明还涉及通过这种4-氨基-3-羟基环己基-1,5-二烯-1-羧酸（3,4-CHA）的共同作用生产合成[3R，4R] -4-氨基-3-羟基环己-1,5-二烯-1-羧酸（3,4-CHA）能够将等分子酸转化为[5S，6S] -5,6二羟基环己-1,3-二烯-1-羧酸（2,3-CHD），优选吩嗪生物合成蛋白PhzD的酶的酶，包括4-脱氧胸苷酸合酶回收3,4-CHA。本发明还涉及用于任何这些方法的表达载体和宿主细胞。本发明还涉及3,4-CHA作为催化活性产物，特别是作为手性催化剂的用途。本发明最终涉及从3,4-CHA合成磷酸奥司他韦。

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