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首页> 外文期刊>Applied and Environmental Microbiology >Modulation of Chaperone Gene Expression in Mutagenized Saccharomyces cerevisiae Strains Developed for Recombinant Human Albumin Production Results in Increased Production of Multiple Heterologous Proteins
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Modulation of Chaperone Gene Expression in Mutagenized Saccharomyces cerevisiae Strains Developed for Recombinant Human Albumin Production Results in Increased Production of Multiple Heterologous Proteins

机译：突变的酿酒酵母菌株的伴侣蛋白基因表达的调控为重组人白蛋白生产结果导致多种异源蛋白产量增加

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摘要

The yeast Saccharomyces cerevisiae has been successfully established as a commercially viable system for the production of recombinant proteins. Manipulation of chaperone gene expression has been utilized extensively to increase recombinant protein production from S. cerevisiae, focusing predominantly on the products of the protein disulfide isomerase gene PDI1 and the hsp70 gene KAR2. Here we show that the expression of the genes SIL1, LHS1, JEM1, and SCJ1, all of which are involved in regulating the ATPase cycle of Kar2p, is increased in a proprietary yeast strain, developed by several rounds of random mutagenesis and screening for increased production of recombinant human albumin (rHA). To establish whether this expression contributes to the enhanced-production phenotype, these genes were overexpressed both individually and in combination. The resultant strains showed significantly increased shake-flask production levels of rHA, granulocyte-macrophage colony-stimulating factor, and recombinant human transferrin.
机译：酵母酿酒酵母已成功建立为商业上可用于生产重组蛋白的系统。伴侣基因表达的操纵已被广泛用于增加酿酒酵母的重组蛋白产量，主要集中在蛋白二硫键异构酶基因PDI1和hsp70基因KAR2的产物上。在这里，我们显示在专有酵母菌株中，所有参与调节Kar2p ATPase循环的基因SIL1，LHS1，JEM1和SCJ1的表达均增加了，该菌株由几轮随机诱变开发并筛选出重组人白蛋白（rHA）的生产。为了确定该表达是否有助于增加产量的表型，这些基因被单独或组合过表达。所得菌株显示出rHA，粒细胞-巨噬细胞集落刺激因子和重组人转铁蛋白的摇瓶生产水平显着提高。

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