title: The fungal α-aminoadipate pathway for lysine biosynthesis requires two enzymes of the aconitase family for the isomerization of homocitrate to homoisocitrate.
abstract: Fungi produce α-aminoadipate, a precursor for penicillin and lysine via the α-aminoadipate pathway. Despite the biotechnological importance of this pathway, the essential isomerization of homocitrate via homoaconitate to homoisocitrate has hardly been studied. Therefore, we analysed the role of homoaconitases and aconitases in this isomerization. Although we confirmed an essential contribution of homoaconitases from Saccharomyces cerevisiae and Aspergillus fumigatus, these enzymes only catalysed the interconversion between homoaconitate and homoisocitrate. In contrast, aconitases from fungi and the thermophilic bacterium Thermus thermophilus converted homocitrate to homoaconitate. Additionally, a single aconitase appears essential for energy metabolism, glutamate and lysine biosynthesis in respirating filamentous fungi, but not in the fermenting yeast S. cerevisiae that possesses two contributing aconitases. While yeast Aco1p is essential for the citric acid cycle and, thus, for glutamate synthesis, Aco2p specifically and exclusively contributes to lysine biosynthesis. In contrast, Aco2p homologues present in filamentous fungi were transcribed, but enzymatically inactive, revealed no altered phenotype when deleted and did not complement yeast aconitase mutants. From these results we conclude that the essential requirement of filamentous fungi for respiration versus the preference of yeasts for fermentation may have directed the evolution of aconitases contributing to energy metabolism and lysine biosynthesis.
authors.affiliation: Microbial Biochemistry and Physiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knoell-Institute, Beutenbergstr. 11a, 07745 Jena, Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Fazius
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shelest
authors.forename: Peter
authors.initials: P
authors.lastname: Gebhardt
authors.forename: Matthias
authors.initials: M
authors.lastname: Brock
mesh_terms: D015074:2-Aminoadipic Acid / Q000378:metabolism*; D000154:Aconitate Hydratase / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics; D004734:Energy Metabolism; D005658:Fungi / Q000201:enzymology* / Q000378:metabolism*; D008239:Lysine / Q000096:biosynthesis*; D014233:Tricarboxylic Acids / Q000378:metabolism*
chemical_list: D014233:Tricarboxylic Acids; C517550:homoisocitric acid; D015074:2-Aminoadipic Acid; C028143:homocitric acid; D000154:Aconitate Hydratase; D008239:Lysine