The Aspergillus nidulans pyruvate dehydrogenase kinases are essential to integrate carbon source metabolism


Ries, Laure Nocolas Annick and de Assis, Leandro José and Rodrigues, Fernando José Santos and Caldana, Camila and Rocha, Maria Campos and Malavazi, Iran and Bayram, Ozgur and Goldman, Gustavo H. (2018) The Aspergillus nidulans pyruvate dehydrogenase kinases are essential to integrate carbon source metabolism. G3, 8 (7). pp. 2445-2463. ISSN 2160-1836

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Abstract

The pyruvate dehydrogenase complex (PDH), that converts pyruvate to acetyl-coA, is regulated by pyruvate dehydrogenase kinases (PDHK) and phosphatases (PDHP) that have been shown to be important for morphology, pathogenicity and carbon source utilization in different fungal species. The aim of this study was to investigate the role played by the three PDHKs PkpA, PkpB and PkpC in carbon source utilization in the reference filamentous fungus Aspergillus nidulans, in order to unravel regulatory mechanisms which could prove useful for fungal biotechnological and biomedical applications. PkpA and PkpB were shown to be mitochondrial whereas PkpC localized to the mitochondria in a carbon sourcedependent manner. Only PkpA was shown to regulate PDH activity. In the presence of glucose, deletion of pkpA and pkpC resulted in reduced glucose utilization, which affected carbon catabolite repression (CCR) and hydrolytic enzyme secretion, due to de-regulated glycolysis and TCA cycle enzyme activities. Furthermore, PkpC was shown to be required for the correct metabolic utilization of cellulose and acetate. PkpC negatively regulated the activity of the glyoxylate cycle enzyme isocitrate lyase (ICL), required for acetate metabolism. In summary, this study identified PDHKs important for the regulation of central carbon metabolism in the presence of different carbon sources, with effects on the secretion of biotechnologically important enzymes and carbon source-related growth. This work demonstrates how central carbon metabolism can affect a variety of fungal traits and lays a basis for further investigation into these characteristics with potential interest for different applications.

Item Type: Article
Additional Information: Published under a Creative Commons Attribution 4.0 International license: https://creativecommons.org/licenses/by/4.0/. Cite as: The Aspergillus nidulans Pyruvate Dehydrogenase Kinases Are Essential To Integrate Carbon Source Metabolism View ORCID ProfileLaure Nicolas Annick Ries, View ORCID ProfileLeandro José de Assis, Fernando José Santos Rodrigues, Camila Caldana, Marina Campos Rocha, View ORCID ProfileIran Malavazi, Özgür Bayram and Gustavo H. Goldman G3: Genes, Genomes, Genetics July 1, 2018 vol. 8 no. 7 2445-2463; https://doi.org/10.1534/g3.118.200411. We would like to thank the Science foundation Ireland (SCI) for supporting quantitative protein mass spectrometry facilities and the Laboratory of Metabolomics (LabMET) at the National Centre for Research in Energy and Materials (CNPEM) for providing metabolome analysis facilities. We would like to thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant numbers 2016/07870-9 for GHG and 2014/00789-6 for LJA), the Science Foundation Ireland (SCI, grant number 13/CDA/2142 for OB) for providing financial support. The funding agencies had no role in study design, data collection and interpretation.
Keywords: Aspergillus nidulans; Carbon catabolite repression; Carbon source utilization and regulation; Pyruvate dehydrogenase kinases;
Academic Unit: Faculty of Science and Engineering > Biology
Item ID: 9671
Identification Number: 10.1534/g3.118.200411
Depositing User: Suzanne Redmond Maloco
Date Deposited: 17 Jul 2018 14:42
Journal or Publication Title: G3
Publisher: Genetics Society of America
Refereed: Yes
Funders: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Science Foundation Ireland (SFI)
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