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    Bioprocess for preparing 7-ACA and 7-ADAC
    2.
    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。

    Extensible architecture for versioning APIs
    5.
    发明授权
    Extensible architecture for versioning APIs 失效
    用于版本API的可扩展架构

    公开(公告)号：US07610316B2

    公开(公告)日：2009-10-27

    申请号：US10935350

    申请日：2004-09-07

    申请人： Bradley J. Bartz ,  Michael R. Santoro ,  Christopher G. Kaler ,  Zachary L. Anderson ,  Christopher D. Reeves

    发明人： Bradley J. Bartz ,  Michael R. Santoro ,  Christopher G. Kaler ,  Zachary L. Anderson ,  Christopher D. Reeves

    IPC分类号： G06F12/00 ,  G06F17/00 ,  G06F9/44

    CPC分类号： G06F8/60 ,  G06F9/44536 ,  Y10S707/99953 ,  Y10S707/99954

    摘要： Some large software development projects need more than one versioning system to accommodate not only a diversity of document formats and data types, but also the geographic diversity of its programmers. However, having more than one versioning system is generally very expensive. A major factor in this expense is the requirement for a separate application program interface (API) for each separate versioning system. Accordingly, the inventors devised an exemplary API architecture that can be extended with “plug-in”protocol providers to include virtually any number of separate version stores or versioning systems. The exemplary architecture includes a generic command parser and a command dispatcher. The command dispatcher operatively couples to one or more protocol providers, each coupled to at least one version store. Inclusion of the OLE DB-compliant interface and the command parser in the exemplary embodiment saves the protocol providers the effort and expense of replicating these features, thereby reducing the cost of adding version stores.

    摘要翻译： 一些大型软件开发项目需要一个以上的版本控制系统，以适应文档格式和数据类型的多样性，同时也适应其程序员的地理多样性。 但是，拥有多个版本控制系统通常非常昂贵。 这个费用的一个主要因素是每个单独的版本控制系统需要一个单独的应用程序接口（API）。 因此，发明人设计了可以用“插件”协议提供者来扩展的示例性API架构，以实际包括任何数量的单独的版本存储或版本控制系统。 示例性架构包括通用命令解析器和命令分派器。 命令调度器可操作地耦合到一个或多个协议提供者，每个协议提供者耦合到至少一个版本存储。 在示例性实施例中包括OLE DB兼容接口和命令解析器保存协议提供者复制这些特征的努力和费用，从而降低添加版本存储的成本。

    Recombinant bioprocess for the preparation of 7-amino cephalosporanic acid (7-ACA)
    7.
    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。

    Biosynthetic gene cluster for ambruticins and the encoded proteins
    8.
    发明授权
    Biosynthetic gene cluster for ambruticins and the encoded proteins 有权
    氨基丁酸和编码蛋白的生物合成基因簇

    公开(公告)号：US07332576B2

    公开(公告)日：2008-02-19

    申请号：US11075185

    申请日：2005-03-07

    申请人： Christopher D. Reeves ,  Bryan Julien ,  Ralph C. Reid

    发明人： Christopher D. Reeves ,  Bryan Julien ,  Ralph C. Reid

    IPC分类号： C07K1/00

    CPC分类号： C12N15/52 ,  C12P17/06

    摘要： Domains of ambruticin polyketide synthase and modification enzymes and polynucleotides encoding them are provided. Methods to prepare ambruticin in pharmaceutically useful quantities are described, as are methods to prepare ambruticin analogs and other polyketides using the polynucleotides encoding ambruticin synthase domains or modifying enzymes.

    摘要翻译： 提供了ambruticin聚酮化合物合酶和修饰酶的结构域以及编码它们的多核苷酸。 描述了以药学上可用的量制备氨溴妥坦的方法，以及使用编码氨基丁酸合酶结构域或修饰酶的多核苷酸制备氨溴霉素类似物和其它聚酮化合物的方法。

    Biosynthetic gene cluster for jerangolids
    9.
    发明授权
    Biosynthetic gene cluster for jerangolids 有权
    jerangolids的生物合成基因簇

    公开(公告)号：US07285405B2

    公开(公告)日：2007-10-23

    申请号：US11109593

    申请日：2005-04-18

    申请人： Christopher D. Reeves ,  Ralph C. Reid

    发明人： Christopher D. Reeves ,  Ralph C. Reid

    IPC分类号： C12N9/00

    CPC分类号： C12N15/52

    摘要： Domains of jerangolid polyketide synthase and modification enzymes and polynucleotides encoding them are provided. Methods to prepare jerangolid in pharmaceutically useful quantities are described, as are methods to prepare jerangolid analogs and other polyketides using the polynucleotides encoding jerangolid synthase domains or modifying enzymes.

    摘要翻译： 提供了jerangolid聚酮化合物合酶的结构域和修饰酶以及编码它们的多核苷酸。 描述了以药学上可用的量制备吉兰根灵的方法，以及使用编码jerangolid合酶结构域或修饰酶的多核苷酸制备庚二酸固体类似物和其它聚酮化合物的方法。

    Bioprocesses for preparing 7-ACA and 7-ADAC
    10.
    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。