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    Methods for producing hyaluronan in a recombinant host cell
    1.
    发明授权
    Methods for producing hyaluronan in a recombinant host cell 有权
    在重组宿主细胞中产生透明质酸的方法

    公开(公告)号：US08574886B2

    公开(公告)日：2013-11-05

    申请号：US13401663

    申请日：2012-02-21

    申请人： Regine Behr ,  William Widner ,  Maria Tang ,  Stephen Brown ,  Leslie Naggiar ,  Linda Sternberg

    发明人： Alan Sloma ,  Regine Behr ,  William Widner ,  Maria Tang ,  David Sternberg ,  Stephen Brown

    IPC分类号： C12N1/20 ,  C12N15/74 ,  C12N15/00 ,  C12P19/04 ,  C12P19/26 ,  C12P19/28 ,  C12P1/00 ,  C12P21/06 ,  C07H21/04

    CPC分类号： C12P19/26 ,  C12N9/1051 ,  C12N15/52

    摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase.

    摘要翻译： 本发明涉及透明质酸的制备方法，其包括：（a）在适于产生透明质酸的条件下培养芽孢杆菌属宿主细胞，其中所述芽孢杆菌宿主细胞包含可操作地连接的透明质酸合酶编码序列的核酸构建体 涉及透明质酸合酶编码序列外源的启动子序列; 和（b）从培养基中回收透明质酸。 本发明还涉及编码包含透明质酸合酶基因和UDP-葡萄糖-6-脱氢酶基因的透明质酸合酶操纵子的分离的核酸序列，以及任选地一种或多种选自UDP-葡萄糖焦磷酸化酶基因， UDP-N-乙酰葡糖胺焦磷酸化酶基因和葡萄糖-6-磷酸异构酶基因。 本发明还涉及编码UDP-葡萄糖-6-脱氢酶，UDP-葡萄糖焦磷酸化酶和UDP-N-乙酰葡糖胺焦磷酸化酶的分离的核酸序列。

    Methods for producing hyaluronan in a recombinant host cell
    4.
    发明申请
    Methods for producing hyaluronan in a recombinant host cell 有权
    在重组宿主细胞中产生透明质酸的方法

    公开(公告)号：US20120149067A1

    公开(公告)日：2012-06-14

    申请号：US13401663

    申请日：2012-02-21

    申请人： Alan Sloma ,  Leslie Naggiar ,  Regine Behr ,  William Widner ,  Maria Tang ,  David Sternberg ,  Linda Sternberg ,  Stephen Brown

    发明人： Alan Sloma ,  Leslie Naggiar ,  Regine Behr ,  William Widner ,  Maria Tang ,  David Sternberg ,  Linda Sternberg ,  Stephen Brown

    IPC分类号： C12P19/28

    CPC分类号： C12P19/26 ,  C12N9/1051 ,  C12N15/52

    摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase

    摘要翻译： 本发明涉及透明质酸的制备方法，其包括：（a）在适于产生透明质酸的条件下培养芽孢杆菌属宿主细胞，其中所述芽孢杆菌宿主细胞包含可操作地连接的透明质酸合酶编码序列的核酸构建体 涉及透明质酸合酶编码序列外源的启动子序列; 和（b）从培养基中回收透明质酸。 本发明还涉及编码包含透明质酸合酶基因和UDP-葡萄糖-6-脱氢酶基因的透明质酸合酶操纵子的分离的核酸序列，以及任选地一种或多种选自UDP-葡萄糖焦磷酸化酶基因， UDP-N-乙酰葡糖胺焦磷酸化酶基因和葡萄糖-6-磷酸异构酶基因。 本发明还涉及编码UDP-葡萄糖-6-脱氢酶，UDP-葡萄糖焦磷酸化酶和UDP-N-乙酰葡糖胺焦磷酸化酶的分离的核酸序列

    Methods for producing hyaluronan in a recombinant host cell
    5.
    发明授权
    Methods for producing hyaluronan in a recombinant host cell 有权
    在重组宿主细胞中产生透明质酸的方法

    公开(公告)号：US08137951B2

    公开(公告)日：2012-03-20

    申请号：US13084230

    申请日：2011-04-11

    申请人： Alan Sloma ,  Leslie Naggiar, legal representative ,  Regine Behr ,  William Widner ,  Maria Tang ,  David Sternberg ,  Linda Sternberg, legal representative ,  Stephen Brown

    发明人： Alan Sloma ,  Regine Behr ,  William Widner ,  Maria Tang ,  David Sternberg ,  Stephen Brown

    IPC分类号： C12N1/20 ,  C12N15/74 ,  C12N15/00 ,  C12P21/00 ,  C12P9/26 ,  C12P1/00 ,  C12N9/00 ,  C12N9/24 ,  C12N9/88 ,  C07H21/04

    CPC分类号： C12P19/26 ,  C12N9/1051 ,  C12N15/52

    摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase.

    摘要翻译： 本发明涉及透明质酸的制备方法，其包括：（a）在适于产生透明质酸的条件下培养芽孢杆菌属宿主细胞，其中所述芽孢杆菌宿主细胞包含可操作地连接的透明质酸合酶编码序列的核酸构建体 涉及透明质酸合酶编码序列外源的启动子序列; 和（b）从培养基中回收透明质酸。 本发明还涉及编码包含透明质酸合酶基因和UDP-葡萄糖-6-脱氢酶基因的透明质酸合酶操纵子的分离的核酸序列，以及任选地一种或多种选自UDP-葡萄糖焦磷酸化酶基因， UDP-N-乙酰葡糖胺焦磷酸化酶基因和葡萄糖-6-磷酸异构酶基因。 本发明还涉及编码UDP-葡萄糖-6-脱氢酶，UDP-葡萄糖焦磷酸化酶和UDP-N-乙酰葡糖胺焦磷酸化酶的分离的核酸序列。

    Methods for producing hyaluronan in a recombinant host cell
    6.
    发明申请
    Methods for producing hyaluronan in a recombinant host cell 有权
    在重组宿主细胞中产生透明质酸的方法

    公开(公告)号：US20110014662A1

    公开(公告)日：2011-01-20

    申请号：US12891548

    申请日：2010-09-27

    申请人： Alan Sloma ,  Leslie Naggiar ,  Regine Behr ,  William Widner ,  Maria Tang ,  David Sternberg ,  Linda Sternberg ,  Stephen Brown

    发明人： Alan Sloma ,  Leslie Naggiar ,  Regine Behr ,  William Widner ,  Maria Tang ,  David Sternberg ,  Linda Sternberg ,  Stephen Brown

    IPC分类号： C12P19/04

    CPC分类号： C12P19/26 ,  C12N9/1051 ,  C12N15/52

    摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase

    摘要翻译： 本发明涉及透明质酸的制备方法，其包括：（a）在适于产生透明质酸的条件下培养芽孢杆菌属宿主细胞，其中所述芽孢杆菌宿主细胞包含可操作地连接的透明质酸合酶编码序列的核酸构建体 涉及透明质酸合酶编码序列外源的启动子序列; 和（b）从培养基中回收透明质酸。 本发明还涉及编码包含透明质酸合酶基因和UDP-葡萄糖-6-脱氢酶基因的透明质酸合酶操纵子的分离的核酸序列，以及任选的一种或多种选自UDP-葡萄糖焦磷酸化酶基因， UDP-N-乙酰葡糖胺焦磷酸化酶基因和葡萄糖-6-磷酸异构酶基因。 本发明还涉及编码UDP-葡萄糖-6-脱氢酶，UDP-葡萄糖焦磷酸化酶和UDP-N-乙酰葡糖胺焦磷酸化酶的分离的核酸序列

    Methods for producing biological substances in pigment-deficient mutants of bacillus cells
    7.
    发明授权
    Methods for producing biological substances in pigment-deficient mutants of bacillus cells 有权
    在芽孢杆菌细胞色素缺陷突变体中生产生物物质的方法

    公开(公告)号：US08124376B2

    公开(公告)日：2012-02-28

    申请号：US12703550

    申请日：2010-02-10

    申请人： Maria Tang ,  Alan Sloma ,  Leslie Naggiar, legal representative ,  David Sternberg ,  Linda Sternberg, legal representative ,  Regine Behr

    发明人： Maria Tang ,  Alan Sloma ,  David Sternberg ,  Regine Behr

    IPC分类号： C12P21/06

    CPC分类号： C12N9/0077 ,  C07K14/32 ,  C12P1/04 ,  C12P19/00 ,  C12P21/02

    摘要： The present invention relates to methods of producing a heterologous biological substance, comprising: (a) cultivating a mutant of a parent Bacillus cell under conditions conducive for the production of the heterologous biological substance, wherein (i) the mutant cell comprises a first nucleic acid sequence directing synthesis of the heterologous biological substance and a second nucleic acid sequence comprising a modification of at least one of the genes cypX and yvmC, which are involved in the production of a red pigment, and (ii) the mutant cell is deficient in the production of the red pigment compared to the parent Bacillus cell when cultivated under the same conditions; and (b) recovering the heterologous biological substance from the cultivation medium. The present invention also relates to mutants of Bacillus cells and methods for producing the mutants.

    摘要翻译： 本发明涉及产生异源生物物质的方法，其包括：（a）在有利于产生异源生物物质的条件下培养亲本芽孢杆菌细胞的突变体，其中（i）突变细胞包含第一核酸 指导异源生物物质合成的序列和包含参与红色素生产的至少一种基因cypX和yvmC的修饰的第二核酸序列，和（ii）突变细胞在 在相同条件下培养时，与母体芽孢杆菌细胞相比，产生红色素; 和（b）从培养基中回收异源生物物质。 本发明还涉及芽孢杆菌细胞的突变体和产生突变体的方法。

    Methods for producing hyaluronan in a recombinant host cell
    9.
    发明授权
    Methods for producing hyaluronan in a recombinant host cell 有权
    在重组宿主细胞中产生透明质酸的方法

    公开(公告)号：US07811806B2

    公开(公告)日：2010-10-12

    申请号：US10326185

    申请日：2002-12-20

    申请人： Alan Sloma ,  Regine Behr ,  William Widner ,  Maria Tang ,  David Sternberg ,  Stephen Brown

    发明人： Alan Sloma ,  Regine Behr ,  William Widner ,  Maria Tang ,  David Sternberg ,  Stephen Brown

    IPC分类号： C12N1/20 ,  C12N15/74 ,  C12N15/00 ,  C12P21/06 ,  C12P19/04 ,  C12P19/26

    CPC分类号： C12P19/26 ,  C12N9/1051 ,  C12N15/52

    摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase.

    摘要翻译： 本发明涉及透明质酸的制备方法，其包括：（a）在适于产生透明质酸的条件下培养芽孢杆菌属宿主细胞，其中所述芽孢杆菌宿主细胞包含可操作地连接的透明质酸合酶编码序列的核酸构建体 涉及透明质酸合酶编码序列外源的启动子序列; 和（b）从培养基中回收透明质酸。 本发明还涉及编码包含透明质酸合酶基因和UDP-葡萄糖-6-脱氢酶基因的透明质酸合酶操纵子的分离的核酸序列，以及任选地一种或多种选自UDP-葡萄糖焦磷酸化酶基因， UDP-N-乙酰葡糖胺焦磷酸化酶基因和葡萄糖-6-磷酸异构酶基因。 本发明还涉及编码UDP-葡萄糖-6-脱氢酶，UDP-葡萄糖焦磷酸化酶和UDP-N-乙酰葡糖胺焦磷酸化酶的分离的核酸序列。

    Methods for producing biological substances in pigment-deficient mutants of bacillus cells
    10.
    发明授权
    Methods for producing biological substances in pigment-deficient mutants of bacillus cells 有权
    在芽孢杆菌细胞色素缺陷突变体中生产生物物质的方法

    公开(公告)号：US07666625B2

    公开(公告)日：2010-02-23

    申请号：US12331323

    申请日：2008-12-09

    申请人： Maria Tang ,  Alan Sloma ,  David Sternberg ,  Linda Sternberg, legal representative ,  Regine Behr

    发明人： Maria Tang ,  Alan Sloma ,  David Sternberg ,  Regine Behr

    IPC分类号： C12P21/06

    CPC分类号： C12N9/0077 ,  C07K14/32 ,  C12P1/04 ,  C12P19/00 ,  C12P21/02

    摘要： The present invention relates to methods of producing a heterologous biological substance, comprising: (a) cultivating a mutant of a parent Bacillus cell under conditions conducive for the production of the heterologous biological substance, wherein (i) the mutant cell comprises a first nucleic acid sequence directing synthesis of the heterologous biological substance and a second nucleic acid sequence comprising a modification of at least one of the genes cypX and yvmC, which are involved in the production of a red pigment, and (ii) the mutant cell is deficient in the production of the red pigment compared to the parent Bacillus cell when cultivated under the same conditions; and (b) recovering the heterologous biological substance from the cultivation medium. The present invention also relates to mutants of Bacillus cells and methods for producing the mutants.

    摘要翻译： 本发明涉及产生异源生物物质的方法，其包括：（a）在有利于产生异源生物物质的条件下培养亲本芽孢杆菌细胞的突变体，其中（i）突变细胞包含第一核酸 指导异源生物物质合成的序列和包含参与红色素生产的至少一种基因cypX和yvmC的修饰的第二核酸序列，和（ii）突变细胞在 在相同条件下培养时，与母体芽孢杆菌细胞相比，产生红色素; 和（b）从培养基中回收异源生物物质。 本发明还涉及芽孢杆菌细胞的突变体和产生突变体的方法。