title: Improvement of foreign-protein production in Aspergillus niger var. awamori by constitutive induction of the unfolded-protein response.
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.
authors.affiliation: VTT Biotechnology, Espoo, Finland. mari.valkonen@vtt.fi
authors.forename: Mari
authors.initials: M
authors.lastname: Valkonen
authors.forename: Michael
authors.initials: M
authors.lastname: Ward
authors.forename: Huaming
authors.initials: H
authors.lastname: Wang
authors.forename: Merja
authors.initials: M
authors.lastname: Penttilä
authors.forename: Markku
authors.initials: M
authors.lastname: Saloheimo
mesh_terms: D000818:Animals; D001234:Aspergillus niger / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D001487:Basidiomycota / Q000201:enzymology / Q000235:genetics; D002417:Cattle; D012085:Chymosin / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D042845:Laccase / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014170:Transformation, Genetic
chemical_list: D003470:Culture Media; D005656:Fungal Proteins; D014157:Transcription Factors; D042845:Laccase; D012085:Chymosin