Effective lead selection for improved protein production in Aspergillus niger basedon integrated genomics
Author:
Denise I. Jacobs, Maurien M.A. Olsthoorn, Isabelle Maillet, Michiel Akeroyd, Stefaan Breestraat,Serge Donkers, Rob A.M. van der Hoeven, Cees A.M.J.J. van den Hondel, Rolf Kooistra,Thomas Lapointe, Hildegard Menke, Rogier Meulenberg, Marijke Misset, Wally H. Müller,Noël N.M.E. van Peij, Arthur Ram, Sabrina Rodriguez, Marc S. Roelofs, Johannes A. Roubos,Marcel W.E.M. van Tilborg, Arie J. Verkleij, Herman J. Pel, Hein Stam, Cees M.J. Sagt
Date: 8 April 2009
Abstract:
The filamentous fungus Aspergillus niger is widely exploited for industrial production of enzymes andorganic acids. An integrated genomics approach was developed to determine cellular responses of A. nigerto protein production in well-controlled fermentations. Different protein extraction methods in combinationwith automated sample processing and protein identification allowed quantitative analysis of 898proteins. Three different enzyme overproducing strains were compared to their isogenic fungal hoststrains. Clear differences in response to the amount and nature of the overproduced enzymes wereobserved. The corresponding genes of the differentially expressed proteins were studied using transcriptomics.Genes that were up-regulated both at the proteome and transcriptome level were selected as leadsfor generic strain improvement. Up-regulated proteins included proteins involved in carbon and nitrogenmetabolism as well as (oxidative) stress response, and proteins involved in protein folding and endoplasmicreticulum-associated degradation (ERAD). Reduction of protein degradation through the removal ofthe ERAD factor doaA combined with overexpression of the oligosaccharyl transferase sttC in A. niger overproducingb-glucuronidase (GUS) strains indeed resulted in a small increase in GUS expression.
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