利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

11 条记录 (耗时 0.027 秒)

    Recombinant bioprocess for the preparation of 7-amino cephalosporanic acid (7-ACA)
    1.
    发明授权
    Recombinant bioprocess for the preparation of 7-amino cephalosporanic acid (7-ACA) 失效
    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。

    Bioprocesses for preparing 7-ACA and 7-ADAC
    3.
    发明授权
    Bioprocesses for preparing 7-ACA and 7-ADAC 失效
    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。

    Bioprocess for preparing 7-ACA and 7-ADAC
    4.
    发明授权
    Bioprocess for preparing 7-ACA and 7-ADAC 失效
    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。

    Biosynthetic production of 7-[1',2',6',7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)-hydroxy-1' (S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid (triol acid)
    9.
    发明授权
    Biosynthetic production of 7-[1',2',6',7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)-hydroxy-1' (S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid (triol acid) 失效
    7- [1'，2'，6'，7'，8'，8a'（R） - 六氢-2'（S），6'（R） - 二甲基-8'（S） - 羟基 -1'（S） - 萘基] -3（R），5（R） - 二羟基庚酸（三醇酸）

    公开(公告)号：US5223415A

    公开(公告)日：1993-06-29

    申请号：US832545

    申请日：1992-02-07

    申请人： Michael J. Conder ,  Steven J. Cianciosi ,  William H. Cover ,  Rebecca L. Dabora ,  Eric T. Pisk ,  Robert W. Stieber ,  Bogdan Tehlewitz ,  Gregory L. Tewalt

    发明人： Michael J. Conder ,  Steven J. Cianciosi ,  William H. Cover ,  Rebecca L. Dabora ,  Eric T. Pisk ,  Robert W. Stieber ,  Bogdan Tehlewitz ,  Gregory L. Tewalt

    IPC分类号： C07C59/46 ,  C12P7/42 ,  C12P17/06 ,  C12R1/645 ,  C12R1/66 ,  C12R1/77 ,  C12R1/78 ,  C12R1/785 ,  C12R1/88

    CPC分类号： C12P17/06 ,  C07C59/46 ,  C12P7/42

    摘要： Biosynthetic production of 7-[1',2',6',-7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)-hydroxy-1'(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid, "triol acid", is accomplished by enzymatic hydrolysis of lovastatin acid or a salt thereof, by treating it with Clonostachys compactiuscula ATCC 38009 or ATCC 74178, or mutants thereof, or a cell-free extract derived therefrom, or a hydrolase derived therefrom. The triol acid and its lactone form are both inhibitors of HMG-CoA reductase and thus useful as anti-hypercholesterolemic agents, and may also serve as intermediates for preparation of other HMG-CoA reductase inhibitors. Also, in the synthesis of simvastatin by direct methylation of lovastatin, selective hydrolysis of residual lovastatin salt by treatment with Clonostachys compactiuscula ATCC 38009 or ATCC 74178 or mutants thereof or a cell-free extract derived therefrom, or a hydrolase derived therefrom yields the "triol" salt which can be easily separated from simvastatin.

    摘要翻译： 7- [1'，2'，6'，-7'，8'，8a'（R） - 六氢-2'（S），6'（R） - 二甲基-8'（S） - 羟基-1'（S） - 萘基] -3（R），5（R） - 二羟基庚酸，“三醇酸”是通过洛伐他汀酸或其盐的酶水解，通过用克隆氏菌（Clonostachys compactiuscula）ATCC 38009 或ATCC 74178，或其突变体，或由其衍生的无细胞提取物或由其衍生的水解酶。 三醇酸及其内酯形式均为HMG-CoA还原酶的抑制剂，因此可用作抗高胆固醇血症药，也可用作制备其他HMG-CoA还原酶抑制剂的中间体。 此外，在通过洛伐他汀的直接甲基化合成辛伐他汀的情况下，通过用克隆氏菌（Clonostachys compactiuscula）ATCC 38009或ATCC 74178或其突变体或由其衍生的无细胞提取物或其衍生的水解酶进行选择性水解残留的洛伐他汀盐，得到“三醇 “盐可以很容易地与辛伐他汀分离。