Transcriptome Analysis of Recombinant Protein Secretion by Aspergillus nidulans and the Unfolded-Protein Response In Vivo
Transcriptome Analysis of Recombinant Protein Secretion by Aspergillus nidulans and the Unfolded-Protein Response In Vivo
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DOI：
10.1128/aem.71.5.2737-2747.2005
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发表时间：
2005-05
影响因子：
4.4
通讯作者：
Andrew H. Sims;M. E. Gent;K. Lanthaler;N. Dunn-Coleman;S. Oliver;G. Robson
中科院分区：
文献类型：
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作者：
Andrew H. Sims;M. E. Gent;K. Lanthaler;N. Dunn-Coleman;S. Oliver;G. Robson
丝状真菌具有产生大量分泌蛋白的高能力，这一特性已被用于重组蛋白的商业生产。然而，分泌途径，这是关键的细胞外蛋白质的生产，是相当差的特点，在丝状真菌相比，酵母。我们报告的重组蛋白分泌的影响，构巢曲霉基因表达水平直接比较牛凝乳酶生产菌株与其亲本野生型菌株在连续培养中，通过使用表达序列标签微阵列。这种方法证明了基因表达的变化比通过使用分泌阻断剂模拟蛋白质过量产生的影响时观察到的变化更微妙和具体。过表达分泌的重组蛋白的影响更接近于体内未折叠的蛋白质反应。
ABSTRACT Filamentous fungi have a high capacity for producing large amounts of secreted proteins, a property that has been exploited for commercial production of recombinant proteins. However, the secretory pathway, which is key to the production of extracellular proteins, is rather poorly characterized in filamentous fungi compared to yeast. We report the effects of recombinant protein secretion on gene expression levels in Aspergillus nidulans by directly comparing a bovine chymosin-producing strain with its parental wild-type strain in continuous culture by using expressed sequence tag microarrays. This approach demonstrated more subtle and specific changes in gene expression than those observed when mimicking the effects of protein overproduction by using a secretion blocker. The impact of overexpressing a secreted recombinant protein more closely resembles the unfolded-protein response in vivo.