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Applied and Environmental Microbiology, December 2003, p. 6979-6986, Vol. 69, No. 12
0099-2240/03/$08.00+0     DOI: 10.1128/AEM.69.12.6979-6986.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Mari Valkonen,1* Michael Ward,2 Huaming Wang,2 Merja Penttilä,1 and Markku Saloheimo1

VTT Biotechnology, Espoo, Finland,1 Genencor International, Inc., Palo Alto, California2

Received 9 June 2003/ Accepted 2 September 2003

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.

* Corresponding author. Mailing address: VTT Biotechnology, P.O. Box 1500, FIN-02044 VTT, Finland. Phone: 358-9-456-5825. Fax: 358-9-455-2103. E-mail: mari.valkonen{at}vtt.fi.

Applied and Environmental Microbiology, December 2003, p. 6979-6986, Vol. 69, No. 12
0099-2240/03/$08.00+0     DOI: 10.1128/AEM.69.12.6979-6986.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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