Breaking the silence: protein stabilization uncovers silenced biosynthetic gene clusters in the fungus Aspergillus nidulans

Ref ID: 18446

Author:

Jennifer Gerke, Özgür Bayram, Kirstin Feussner, Manuel Landesfeind, Ivo Feussner, Gerhard Braus

Author address:

Georg-August-University Göttingen

Full conference title:

11 th European Conference on Fungal Genetics

Abstract:

Antimicrobial resistance is spreading but the number of newly discovered antibiotics is declining. The genomes of
filamentous fungi comprise numerous putative genes and gene clusters for chemically and structurally diverse
secondary metabolites which are rarely expressed under laboratory conditions. Previous approaches to activate
these genes were primarily based on artificially targeting the cellular protein synthesis apparatus. Here, we applied
successfully the first alternative approach of genetically impairing the protein degradation apparatus of the model
fungus Aspergillus nidulans by deleting the conserved eukaryotic csnE/CSN5 deneddylase subunit of the COP9
signalosome. This defect in protein degradation results in the activation of a previously silenced gene cluster
comprising an orphaned polyketide synthase (PKS) gene. We identified the direct PKS product as 2,48208;dihydroxy8208;38208;
methyl8208;68208;(28208;oxopropyl)benzaldehyde (DHMBA). The csn5 gene is highly conserved in fungi and therefore, the
deletion of the gene is a feasible novel approach for the identification of new secondary metabolites in
filamentous fungi.

Abstract Number: PS8.3

Conference Year: 2012

Link to conference website: http://www.ecfg.info/images/Abstract_Book_Electronic.pdf

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