Improvement of Foreign-Protein Production in Aspergillus niger var. awamori by Constitutive Induction of the Unfolded-Protein Response

Mari Valkonen, Michael Ward, Huaming Wang, Merja Penttilä, Markku Saloheimo

Research output: Contribution to journalArticleScientificpeer-review

85 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6979-6986
Number of pages8
JournalApplied and Environmental Microbiology
Volume69
Issue number12
DOIs
Publication statusPublished - 1 Dec 2003
MoE publication typeA1 Journal article-refereed

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