公开(公告)号：US06133023A

公开(公告)日：2000-10-17

申请号：US981601

申请日：1997-12-29

申请人： Soeren Michael Madsen ,  Astrid Vrang ,  Jose Arnau ,  Peter Ravn ,  Mads Groenvald Johnsen ,  Hans Israelsen

发明人： Soeren Michael Madsen ,  Astrid Vrang ,  Jose Arnau ,  Peter Ravn ,  Mads Groenvald Johnsen ,  Hans Israelsen

IPC分类号： A23L29/00 ,  C07K14/35 ,  C12N1/21 ,  C12N15/31 ,  C12N15/74 ,  C12N15/00 ,  C12N1/20 ,  C12N7/00 ,  C12P19/34

CPC分类号： C12N15/746 ,  C07K14/35

摘要： Expression vectors capable of being replicated in lactic acid bacterial cells comprising a promoter region comprising (a) a promoter sequence element the function of which is regulatable by an environmental or growth condition factor and (b) at least one further nucleotide sequence element, the position, orientation, presence and/or sequence of which element has a regulatory effect on the expression of a gene operably linked to the promoter region in which vectors the position, orientation, presence and/or sequence of at least one of said elements (a) or (b) is modified relative to the position, orientation, presence and/or sequence of the corresponding non-modified element whereby the expression of the gene is altered, and a lactic acid bacterium which is transformed with such a vector as defined above are provided. The recombinant cells containing such a regulatable or inducible gene expression system are useful as food or feed starter cultures or as strains for the production of gene products such as pharmaceutically or immunologically active compounds including oligo- or polypeptides derived from a Mycobacterium species including M. tuberculosis.

摘要翻译： PCT No.PCT / DK97 / 00341 Sec。 371日期1997年12月29日第 102（e）日期1997年12月29日PCT 1997年8月22日PCT公布。 第WO98 / 10079号公报 日期1998年3月12日能够复制在包含启动子区域的乳酸菌细胞中的表达载体包括（a）启动子序列元件，其功能由环境或生长条件因子调节，和（b）至少一个其它核苷酸 序列元件，哪个元件的位置，取向，存在和/或序列对可操作地连接到启动子区的基因的表达具有调节作用，其中载体中的至少一个的位置，取向，存在和/或序列 所述元件（a）或（b）相对于相应的未修饰元件的位置，取向，存在和/或序列被修饰，从而基因的表达被改变，并且用这种 提供了如上所述的载体。 含有这种可调节或可诱导基因表达系统的重组细胞可用作食物或饲料起始培养物或用作产生基因产物的菌株，例如药学或免疫活性化合物，包括衍生自包括结核分枝杆菌在内的分枝杆菌物种的寡肽或多肽 。

公开(公告)号：US07358067B2

公开(公告)日：2008-04-15

申请号：US09982531

申请日：2001-10-19

申请人： Astrid Vrang ,  Søren Michael Madsen ,  Lars Bredmose ,  Peter Ravn ,  Jose Arnau ,  Mads Gronvald Johnsen ,  Anne Cathrine Steenberg ,  Hans Israelsen

发明人： Astrid Vrang ,  Søren Michael Madsen ,  Lars Bredmose ,  Peter Ravn ,  Jose Arnau ,  Mads Gronvald Johnsen ,  Anne Cathrine Steenberg ,  Hans Israelsen

IPC分类号： C12P21/00 ,  C12N1/21

CPC分类号： C12N15/74 ,  C12N1/00 ,  C12N9/22 ,  C12N15/67

摘要： The invention provides a fed-batch or continuous process for producing heterologous peptides, polypeptides or proteins in lactic acid bacteria, comprising the steps of (i) constructing a recombinant lactic acid bacterium comprising a nucleotide sequence coding for the heterologous peptide, polypeptide or protein, and appropriate regulatory nucleotide sequences such as regulatable promoters and signal peptides to control the expression of the coding sequence and the secretion of gene product, (ii) cultivating the recombinant bacterium under or continuous cultivation conditions to express the gene, and (iii) harvesting the recombinant bacterium or the gene product. Preferably, the cultivation medium is a chemically defined or synthetic medium optionally supplemented with yeast extract.

摘要翻译： 本发明提供了用于在乳酸菌中产生异源肽，多肽或蛋白质的补料分批或连续方法，包括以下步骤：（i）构建重组乳酸菌，其包含编码异源肽，多肽或蛋白质的核苷酸序列， 以及适当的调控核苷酸序列如可调节的启动子和信号肽，以控制编码序列的表达和基因产物的分泌，（ii）在培养条件下或连续培养条件下培养重组细菌以表达基因，和（iii）收获 重组细菌或基因产物。 优选地，培养基是任选地补充有酵母提取物的化学上定义的或合成的培养基。