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1. 发明授权

US5629171A Recombinant bioprocess for the preparation of 7-amino cephalosporanic acid (7-ACA) 失效
标题翻译：用于制备7-氨基头孢菌酸（7-ACA）的重组生物过程
公开(公告)号：US5629171A
公开(公告)日：1997-05-13
申请号：US439404
申请日：1995-05-11
申请人： Michael J. Conder , John A. Rambosek , Phyllis C. McAda , Christopher D. Reeves
发明人： Michael J. Conder , John A. Rambosek , Phyllis C. McAda , Christopher D. Reeves
IPC分类号： C12N1/19 , C07D501/20 , C12N1/15 , C12N9/00 , C12N9/02 , C12N9/10 , C12N15/09 , C12N15/52 , C12N15/54 , C12P20060101 , C12P35/00 , C12P35/06 , C12P37/04 , C12R1/82 , C12N1/16 , C12P35/02
CPC分类号： C12N9/0071 , C12N9/00 , C12N9/1029 , C12P35/00 , C12P37/04 , Y10S435/935
摘要： Important intermediates for preparing cephalosporin antibiotics, 7-amino-cephalosporanic acid (7-ACA) and 7-aminodeacetylcephalosporanic acid (7-ADAC), are prepared by a novel bioprocess in which a transformed Penicillium chrysogenum strain is cultured in the presence of an adipate feedstock to produce adipoyl-6-APA (6-amino penicillanic acid); followed by the in situ expression of the following genes with which the P. chrysogenum has been transformed:1) an expandase gene, whose expression product converts the adipoyl-6-APA by ring expansion to adipoyl-7-ADCA;2) an hydroxylase gene whose expression product converts the 3-methyl side chain of adipoyl-7-ADCA to 3-hydroxymethyl, to give the first product, 7-aminodeacetylcephalosporanic acid (7-ADAC); and3) an acetyltransferase gene whose expression product converts the 3-hydroxymethyl side chain to the 3-acetyloxymethyl side chain of 7-ACA. The final product, 7-ACA, is then prepared by cleavage of the adipoyl side chain using an adipoyl acylase. The entire synthesis, accordingly, is carried out using bioprocesses, and is efficient and economical.
摘要翻译：用于制备头孢菌素抗生素，7-氨基 - 头孢菌酸（7-ACA）和7-氨基脱乙酰头孢菌酸（7-ADAC）的重要中间体是通过新型生物工艺制备的，其中转化的产黄青霉菌株在己二酸存在下培养生产己二酰-6-APA（6-氨基青霉烷酸）的原料; 其次是产生产黄青霉素的以下基因的原位表达：1）扩展酶基因，其表达产物通过环扩展将己二酰基-6-APA转化为己二酰-7-ADCA; 2）表达产物将己二酰-7-ADCA的3-甲基侧链转化为3-羟甲基的羟化酶基因，得到第一产物7-氨基乙酰头孢烷酸（7-ADAC）; 和3）其表达产物将3-羟甲基侧链转化为7-ACA的3-乙酰氧甲基侧链的乙酰转移酶基因。然后通过使用己二酰酰化酶裂解己二酰侧链制备最终产物7-ACA。因此，整个合成使用生物工艺进行，并且是高效和经济的。

2. 发明授权

US6017726A Bioprocesses for preparing 7-ACA and 7-ADAC 失效
标题翻译：用于制备7-ACA和7-ADAC的生物工艺
公开(公告)号：US6017726A
公开(公告)日：2000-01-25
申请号：US839327
申请日：1997-04-17
申请人： Michael J. Conder , John A. Rambosek , Phyllis C. McAda , Christopher D. Reeves
发明人： Michael J. Conder , John A. Rambosek , Phyllis C. McAda , Christopher D. Reeves
IPC分类号： C12N1/19 , C07D501/20 , C12N1/15 , C12N9/00 , C12N9/02 , C12N9/10 , C12N15/09 , C12N15/52 , C12N15/54 , C12P20060101 , C12P35/00 , C12P35/06 , C12P37/04 , C12R1/82 , C12P35/02 , C12N9/84
CPC分类号： C12N9/0071 , C12N9/00 , C12N9/1029 , C12P35/00 , C12P37/04 , Y10S435/935
摘要： A process for making 7-aminodeacetyl-cephalosporanic acid (7-ADAC).
摘要翻译：制备7-氨基脱乙酰基 - 头孢菌酸（7-ADAC）的方法。

3. 发明授权

US6071713A Bioprocesses for preparing 7-ACA and 7-ADAC 失效
标题翻译：用于制备7-ACA和7-ADAC的生物工艺
公开(公告)号：US6071713A
公开(公告)日：2000-06-06
申请号：US340781
申请日：1999-06-28
申请人： Michael J. Conder , John A. Rambosek , Phyllis C. McAda , Christopher D. Reeves
发明人： Michael J. Conder , John A. Rambosek , Phyllis C. McAda , Christopher D. Reeves
IPC分类号： C12N1/19 , C07D501/20 , C12N1/15 , C12N9/00 , C12N9/02 , C12N9/10 , C12N15/09 , C12N15/52 , C12N15/54 , C12P20060101 , C12P35/00 , C12P35/06 , C12P37/04 , C12R1/82 , C12N1/14 , C12N1/20 , C12P35/02
CPC分类号： C12N9/0071 , C12N9/00 , C12N9/1029 , C12P35/00 , C12P37/04 , Y10S435/935
摘要： A bioprocess for preparing adipoyl-7-ACA comprising the steps: (a) transforming cells of a strain of Penicillium chrysogenum which produces isopenicillin N with an expression vector containing DNA encoding an enzyme, having expandase activity capable of accepting adipoyl 6-APA as a substrate, an enzyme having hydroxylase activity capable of accepting adipoyl-7-ADCA as a substrate and an enzyme having acetyl transferase activity capable of accepting adipoyl 7-ADAC as a substrate; (b) culturing the transformed cells from step a) in a suitable culture medium containing an adipate feedstock, wherein said cells produce adipoyl 6-APA; and (c) culturing the transformed cells producing adipoyl 6-APA of step b) under conditions suitable for expression of said DNA encoding enzyme, thereby producing the end product adipoyl-7-ACA.
摘要翻译：一种用于制备己二酰-7-ACA的生物工艺，包括以下步骤：（a）用含有编码酶的DNA的表达载体转化产生异青霉素N的产青霉菌菌株的细胞，其具有能够接受己二酰基6-APA的扩环酶活性底物，能够接受己二酰-7-ADCA作为底物的羟化酶活性的酶和能够接受己二酰基7-ADAC作为底物的乙酰转移酶活性的酶; （b）在含有己二酸原料的合适培养基中培养来自步骤a）的转化细胞，其中所述细胞产生己二酰基6-APA; 和（c）在适于表达所述DNA编码酶的条件下培养产生步骤b）的己二酰基6-APA的转化细胞，从而产生最终产物己二酰-7-ACA。

4. 发明授权

US5559005A Bioprocess for preparing 7-ACA and 7-ADAC 失效
标题翻译：用于制备7-ACA和7-ADAC的生物工艺
公开(公告)号：US5559005A
公开(公告)日：1996-09-24
申请号：US250310
申请日：1994-05-27
申请人： Michael J. Conder , Phyllis C. McAda , John A. Rambosek , Christopher D. Reeves
发明人： Michael J. Conder , Phyllis C. McAda , John A. Rambosek , Christopher D. Reeves
IPC分类号： C12N1/19 , C07D501/20 , C12N1/15 , C12N9/00 , C12N9/02 , C12N9/10 , C12N15/09 , C12N15/52 , C12N15/54 , C12P20060101 , C12P35/00 , C12P35/06 , C12P37/04 , C12R1/82 , C12P35/04 , C12N1/16
CPC分类号： C12N9/0071 , C12N9/00 , C12N9/1029 , C12P35/00 , C12P37/04 , Y10S435/935
摘要： Important intermediates for preparing cephalosporin antibiotics, 7-amino-cephalosporanic acid (7-ACA) and 7-aminodeacetylcephalosporanic acid (7-ADAC), are prepared by a novel bioprocess in which a transformed Penicillium chrysogenum strain is cultured in the presence of an adipate feedstock to produce adipoyl-6-APA (6-amino penicillanic acid); followed by the in situ expression of the following genes with which the P. chrysogenum has been transformed:1) an expandase gene, e.g., from Cephalosporium acremonium, whose expression product converts the adipoyl-6-APA by ring expansion to adipoyl-7-ADCA;2) an hydroxylase gene whose expression product converts the 3-methyl side chain of adipoyl-7-ADCA to 3-hydroxymethyl, to give the first product, 7-aminodeacetylcephalosporanic acid (7-ADAC); and3) an acetyltransferase gene whose expression product converts the 3-hydroxymethyl side chain to the 3-acetyloxymethyl side chain of 7-ACA. The final product, 7-ACA, is then prepared by cleavage of the adipoyl side chain using an adipoyl acylase. The entire synthesis, accordingly, is carried out using bioprocesses, and is efficient and economical.
摘要翻译：用于制备头孢菌素抗生素，7-氨基头孢菌素酸（7-ACA）和7-氨基脱乙酰头孢菌酸（7-ADAC）的重要中间体是通过新型生物工艺制备的，其中转化的产黄青霉菌株在己二酸存在下培养生产己二酰-6-APA（6-氨基青霉烷酸）的原料; 其次是产生产黄青霉的以下基因的原位表达：1）扩增酶基因，例如头孢霉头孢菌，其表达产物通过环扩展将己二酰基-6-APA转化为己二酰-7- ADCA; 2）表达产物将己二酰-7-ADCA的3-甲基侧链转化为3-羟甲基的羟化酶基因，得到第一产物7-氨基乙酰基头孢烷酸（7-ADAC）; 和3）其表达产物将3-羟甲基侧链转化为7-ACA的3-乙酰氧甲基侧链的乙酰转移酶基因。然后通过使用己二酰酰化酶裂解己二酰侧链制备最终产物7-ACA。因此，整个合成使用生物工艺进行，并且是高效和经济的。

5. 发明授权

US5318896A Recombinant expandase bioprocess for preparing 7-aminodesacetoxy cephalosporanic acid (7-ADCA) 失效
标题翻译：用于制备7-氨基脱乙酰氧基头孢菌酸（7-ADCA）的重组扩环酶生物工艺
公开(公告)号：US5318896A
公开(公告)日：1994-06-07
申请号：US933469
申请日：1992-08-28
申请人： Michael J. Conder , Phyllis C. McAda , John A. Rambosek
发明人： Michael J. Conder , Phyllis C. McAda , John A. Rambosek
IPC分类号： C12N15/09 , C12N1/15 , C12N1/19 , C12N1/21 , C12N9/00 , C12N9/02 , C12N9/80 , C12N15/00 , C12N15/52 , C12N15/81 , C12P35/00 , C12P35/02 , C12P35/06 , C12P37/04 , C12R1/38 , C12R1/465 , C12R1/645 , C12R1/82 , C12N9/84
CPC分类号： C12N9/0071 , C12P35/00 , C12P37/04 , Y10S435/935
摘要： An important intermediate for preparing cephalosporin antibiotics, 7-aminodesacetoxy cephalosporanic acid (7-ADCA), is prepared by a novel bioprocess in which a transformed Penicillium chrysogenum strain is cultured in the presence of an adipate feedstock to produce adipoyl-6-APA (6-amino penicillanic acid); and the in situ expression of an expandase gene, e.g., from Streptomyces clavuligerus, with which the P. chrysogenum has been transformed, converts the adipoly-6-APA by ring expansion to adipoyl-7-ADCA. The final product, 7-ADCA, is then prepared by cleavage of the adipoyl side chain using an adipoyl acylase. The entire synthesis, accordingly, is carried out using bioprocesses, and is efficient and economical.
摘要翻译：通过一种新的生物工艺制备了头孢菌素类抗生素7-氨基乙酰氧基头孢菌素酸（7-ADCA）的重要中间体，其中转化的产黄青霉菌株在己二酸原料存在下培养以产生己二酰基-6-APA（6 氨基青霉烷酸）; 并且已经转化了产黄青霉的膨胀酶基因例如来自链霉菌的原位表达通过环扩展转化为己二酰-7-ADCA的adipoly-6-APA。然后通过使用己二酰酰化酶裂解己二酰侧链制备最终产物7-ADCA。因此，整个合成使用生物工艺进行，并且是高效和经济的。

6. 发明授权

US5104800A One-step cephalosporin C amidase enzyme 失效
标题翻译：一步CEPHOROSPORIN C AMIDASE ENZYME
公开(公告)号：US5104800A
公开(公告)日：1992-04-14
申请号：US372399
申请日：1989-06-27
申请人： Mark S. Crawford , David B. Finkelstein , John A. Rambosek
发明人： Mark S. Crawford , David B. Finkelstein , John A. Rambosek
IPC分类号： C12N1/21 , C12N9/80 , C12N15/55 , C12P35/02 , C12R1/11 , C12R1/125
CPC分类号： C12P35/02 , C12N9/80
摘要： A process for the one-step conversion of cephalosporin C and derivatives thereof to the corresponding 7-aminocephalosporanic acid and derivatives comprising treating said cephalosporin C and derivatives with a cephalosporin C amidase enzyme of a recited sequence, the DNA encoding said enzyme, and expression thereof in a suitable host, e.g., Bacillus species under the control of a suitable promoter.

7. 发明授权

US5830733A Nucleic acid molecules encoding phytase and pH2.5 acid phosphatase 失效
标题翻译：编码植酸酶和pH2.5酸性磷酸酶的核酸分子
公开(公告)号：US5830733A
公开(公告)日：1998-11-03
申请号：US609426
申请日：1996-03-01
申请人： Helena K. M. Nevalainen , Marja T. Paloheimo , Arja S. K. Miettinen-Oinonen , Tuula K. Torkkeli , Michael Cantrell , Christopher S. Piddington , John A. Rambosek , Marja K. Turunen , Richard B. Fagerstrom , Christine S. Houston
发明人： Helena K. M. Nevalainen , Marja T. Paloheimo , Arja S. K. Miettinen-Oinonen , Tuula K. Torkkeli , Michael Cantrell , Christopher S. Piddington , John A. Rambosek , Marja K. Turunen , Richard B. Fagerstrom , Christine S. Houston
IPC分类号： C12N15/09 , A23K1/165 , C12N1/15 , C12N9/16 , C12N15/55 , C12N15/80 , C12R1/885 , C12N15/63 , C12P21/02
CPC分类号： C12Y301/03002 , A23K20/189 , C12N15/80 , C12N9/16 , C12Y301/03026 , C07K2319/02
摘要： The present invention provides a nucleic acid molecule encoding a phytase. The present invention also provides a nucleic acid molecule encoding a pH 2.5 acid phosphatase. Also provided are vectors, host cells, and a method of overexpressing phytate degrading enzymes.
摘要翻译：本发明提供编码植酸酶的核酸分子。本发明还提供编码pH 2.5酸性磷酸酶的核酸分子。还提供载体，宿主细胞和过表达植酸降解酶的方法。

8. 发明授权

US5229274A Gene encoding one step cephalosporin C amidase and expression thereof in recombinant bacillus 失效
标题翻译：基因编码一步头孢菌素C酰胺酶及其在重组杆菌中的表达
公开(公告)号：US5229274A
公开(公告)日：1993-07-20
申请号：US819717
申请日：1992-01-13
申请人： Mark S. Crawford , David B. Finkelstein , John A. Rambosek
发明人： Mark S. Crawford , David B. Finkelstein , John A. Rambosek
IPC分类号： C12N1/21 , C12N9/80 , C12N15/55 , C12P35/02
CPC分类号： C12N9/80 , C12P35/02
摘要： A process for the one-step conversion of cephalosporin C and derivatives thereof to the corresponding 7-aminocephalosporanic acid and derivatives comprising treating said cephalosporin C and derivatives with a cephalosporin C amidase enzyme of a recited sequence, the DNA encoding said enzyme, and expression thereof in a suitable host, e.g., Bacillus species under the control of a suitable promoter.
摘要翻译：一种将头孢菌素C及其衍生物一步转化为相应的7-氨基头孢烷酸及其衍生物的方法，其包括用所述序列的头孢菌素C酰胺酶处理所述头孢菌素C和衍生物，编码所述酶的DNA及其表达在合适的宿主中，例如在合适的启动子控制下的芽孢杆菌属物种。

9. 发明授权

US5834286A Recombinant cells that express phytate degrading enzymes in desired ratios 失效
标题翻译：以所需比例表达植酸降解酶的重组细胞
公开(公告)号：US5834286A
公开(公告)日：1998-11-10
申请号：US374652
申请日：1995-05-24
申请人： Helena K. M. Nevalainen , Marja T. Paloheimo , Richard B. Fagerstrom , Arja S. K. Miettinen-Oinonen , Marja K. Turunen , John A. Rambosek , Christopher S. Piddington , Christine S. Houston , Michael A. Cantrell
发明人： Helena K. M. Nevalainen , Marja T. Paloheimo , Richard B. Fagerstrom , Arja S. K. Miettinen-Oinonen , Marja K. Turunen , John A. Rambosek , Christopher S. Piddington , Christine S. Houston , Michael A. Cantrell
IPC分类号： C12N15/09 , A23K1/165 , C12N1/15 , C12N1/21 , C12N9/16 , C12N15/80 , C12R1/685 , C12S3/00
CPC分类号： C12N15/80 , A23K20/189 , C12N9/16
摘要： The present invention provides a recombinant combination strain which is capable of over-expressing at least two different genes under two separate promoters in filamentous fungi. The genes encode phytase and pH 2.5 acid phosphatase. Mixtures containing desired ratios of the two enzymes are prepared by recombinant DNA techniques. The enzyme mixtures show a cooperative effect in the degradation of phytic acid and its salts. The preferred ratios of the two enzymes are from about 3:1 to about 16:1.
摘要翻译： PCT No.PCT / US93 / 07058 Sec。 371日期：1995年5月24日 102（e）日期1995年5月24日PCT提交1993年7月27日PCT公布。公开号WO94 / 03072 日本1994年2月17日本发明提供了能够在丝状真菌中的两种不同启动子下过表达至少两种不同基因的重组组合菌株。基因编码植酸酶和pH 2.5酸性磷酸酶。通过重组DNA技术制备含有所需比例的两种酶的混合物。酶混合物对植酸及其盐的降解具有协同作用。两种酶的优选比例为约3:1至约16:1。

10. 发明授权

US5780292A Production of phytate degrading enzymes in trichoderma 失效
标题翻译：在木霉中生产植酸降解酶
公开(公告)号：US5780292A
公开(公告)日：1998-07-14
申请号：US923724
申请日：1992-07-31
申请人： Helena K. M. Nevalainen , Marja T. Paloheimo , Aria S. K. Miettinen-Oinonen , Tuula K. Torkkeli , Michael Cantrell , Cristopher S. Piddington , John A. Rambosek , Marja K. Turunen , Richard B. Fagerstrom
发明人： Helena K. M. Nevalainen , Marja T. Paloheimo , Aria S. K. Miettinen-Oinonen , Tuula K. Torkkeli , Michael Cantrell , Cristopher S. Piddington , John A. Rambosek , Marja K. Turunen , Richard B. Fagerstrom
IPC分类号： C12N15/09 , A23K1/165 , C12N1/15 , C12N9/16 , C12N15/55 , C12N15/80 , C12R1/885 , C12N1/14 , A23K1/00
CPC分类号： C12Y301/03002 , A23K20/189 , C12N15/80 , C12N9/16 , C12Y301/03026 , C07K2319/02
摘要： A highly efficient overexpression system for phytase and pH 2.5 acid phosphatase in Trichoderma is described. This system results in enzyme compositions that are especially useful in the animal feed industry.
摘要翻译：描述了木霉中植酸酶和pH 2.5酸性磷酸酶的高效过表达系统。该系统产生在动物饲料工业中特别有用的酶组合物。

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