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    Carbon Catabolite Repression in Filamentous Fungi Is Regulated by Phosphorylation of the Transcription Factor CreA


    de Assis, Leandro José and Silva, Lilian Pereira and Bayram, Ozgur and Dowling, Paul and Kniemeyer, Olaf and Krüger, Thomas and Brakhage, Axel A. and Chen, Yingying and Dong, Liguo and Tan, Kaeling and Wong, Koon Ho and Ries, Laure N. A. and Goldman, Gustavo H. and Fischer, Reinhard (2021) Carbon Catabolite Repression in Filamentous Fungi Is Regulated by Phosphorylation of the Transcription Factor CreA. mBio, 12 (1). pp. 1-21. ISSN 2161-2129

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    Abstract

    Filamentous fungi of the genus Aspergillus are of particular interest for biotechnological applications due to their natural capacity to secrete carbohydrate-active enzymes (CAZy) that target plant biomass. The presence of easily metabolizable sugars such as glucose, whose concentrations increase during plant biomass hydrolysis, results in the repression of CAZy-encoding genes in a process known as carbon catabolite repression (CCR), which is undesired for the purpose of large-scale enzyme production. To date, the C2H2 transcription factor CreA has been described as the major CC repressor in Aspergillus spp., although little is known about the role of posttranslational modifications in this process. In this work, phosphorylation sites were identified by mass spectrometry on Aspergillus nidulans CreA, and subsequently, the previously identified but uncharacterized site S262, the characterized site S319, and the newly identified sites S268 and T308 were chosen to be mutated to nonphosphorylatable residues before their effect on CCR was investigated. Sites S262, S268, and T308 are important for CreA protein accumulation and cellular localization, DNA binding, and repression of enzyme activities. In agreement with a previous study, site S319 was not important for several here-tested phenotypes but is key for CreA degradation and induction of enzyme activities. All sites were shown to be important for glycogen and trehalose metabolism. This study highlights the importance of CreA phosphorylation sites for the regulation of CCR. These sites are interesting targets for biotechnological strain engineering without the need to delete essential genes, which could result in undesired side effects.

    Item Type: Article
    Keywords: CreA; carbon catabolite repression; xylanase; biofuels; Aspergillus nidulans;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 16216
    Identification Number: https://doi.org/10.1128/mBio.03146-20
    Depositing User: Ozgur Bayram
    Date Deposited: 29 Jun 2022 11:57
    Journal or Publication Title: mBio
    Publisher: American Society for Microbiology
    Refereed: Yes
    URI:

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