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Applied and Environmental Microbiology, May 2005, p. 2737-2747, Vol. 71, No. 5
0099-2240/05/$08.00+0     doi:10.1128/AEM.71.5.2737-2747.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Transcriptome Analysis of Recombinant Protein Secretion by Aspergillus nidulans and the Unfolded-Protein Response In Vivo

Andrew H. Sims,1 Manda E. Gent,1 Karin Lanthaler, Nigel S. Dunn-Coleman,2 Stephen G. Oliver,1* and Geoffrey D. Robson1

Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom,1 Genencor International Inc., 925 Page Mill Road, Palo Alto, California 943042

Received 7 October 2004/ Accepted 9 December 2004

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.

* Corresponding author. Mailing address: Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom. Phone: 44 (0) 161 275 1578. Fax: 44 (0) 161 275 1505. E-mail: steve.oliver{at}manchester.ac.uk.

Applied and Environmental Microbiology, May 2005, p. 2737-2747, Vol. 71, No. 5
0099-2240/05/$08.00+0     doi:10.1128/AEM.71.5.2737-2747.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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