Improvement of Foreign-Protein Production in Aspergillus niger var. awamori by Constitutive Induction of the Unfolded-Protein Response
Improvement of Foreign-Protein Production in Aspergillus niger var. awamori by Constitutive Induction of the Unfolded-Protein Response
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DOI：
10.1128/aem.69.12.6979-6986.2003
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发表时间：
2003-12
影响因子：
4.4
通讯作者：
M. Valkonen;M. Ward;Huaming Wang;M. Penttilä;M. Saloheimo
中科院分区：
文献类型：
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作者：
M. Valkonen;M. Ward;Huaming Wang;M. Penttilä;M. Saloheimo
摘要未折叠蛋白反应（UPR）是指在未折叠蛋白向内质网（ER）积累过程中，内质网（ER）驻留的伴侣蛋白和折叠酶基因以及许多其他参与分泌功能的基因的上调。单个折叠酶和分子伴侣的过表达已被用于尝试改善不同生产系统中的蛋白质生产。我们在这里描述了一种新的策略，以提高外源蛋白的生产。我们表明，组成型诱导的UPR途径在尼日尔曲霉变种。awamori可以通过表达转录因子hacA的活化形式来实现。这种诱导提高了生产的变色栓菌漆酶高达7倍，牛前凝乳酶高达2.8倍，在这个生物技术上的重要真菌。通过分析新A.尼日尔湾awamori基因参与不同的分泌功能。这揭示了酿酒酵母中相应研究的相似性和差异。
ABSTRACT Unfolded-protein response (UPR) denotes the upregulation of endoplasmic reticulum (ER)-resident chaperone and foldase genes and numerous other genes involved in secretory functions during the accumulation of unfolded proteins into the ER. Overexpression of individual foldases and chaperones has been used in attempts to improve protein production in different production systems. We describe here a novel strategy to improve foreign-protein production. We show that the constitutive induction of the UPR pathway in Aspergillus niger var. awamori can be achieved by expressing the activated form of the transcription factor hacA. This induction enhances the production of Trametes versicolor laccase by up to sevenfold and of bovine preprochymosin by up to 2.8-fold in this biotechnically important fungus. The regulatory range of UPR was studied by analyzing the mRNA levels of novel A. niger var. awamori genes involved in different secretory functions. This revealed both similarities and differences to corresponding studies in Saccharomyces cerevisiae.