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

Laure Nicolas Ries 1 Leandro Jose de Assis 1 Fernando Jose Santos Rodrigues 2 Camila Caldana 3 Marina Campos Rocha 4 Iran Malavazi 4 Ozgur Bayram 5 Gustavo Henrique Goldman 1
1Faculty of Pharmaceutical Sciences, University of Sao Paulo, Ribeirao Preto, Brazil
2Instituto de Investigação em Ciências da Vida e Saúde, University of Minho, Braga, Portugal
3Laboratório Nacional de Ciência e Tecnologia do Bioetanol, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, Brazil
4Department of Genetics and Evolution, Federal University of Sao Carlos, Sao Carlos, Brazil
5Biology Department, Maynooth University, Maynooth, Ireland

The pyruvate dehydrogenase complex (PDH), that converts acety-coA to pyruvate, is regulated by a consortium of pyruvate dehydrogenase kinases (PDHK) and phosphatases (PDHP) that have been shown to be important for morphology, pathogenicity and carbon source utilisation in different fungal species. The aim of this study was to investigate the role played by the three PDHKs PkpA, PkpB and PkpC in glucose, cellulose and acetate utilisation in the reference filamentous fungus Aspergillus nidulans, in order to unravel regulatory mechanisms which could prove useful for fungal biotechnological and biomedical applications. All three PDHKs were shown to be mitochondrial with PkpA positively regulating PDH activity. In the presence of glucose, PkpA and PkpC function in the same pathway and deletion of the respective genes resulted in reduced glucose utilisation, 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 utilisation 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.

Financial support: FAPESP and CNPq