title: Role of the Fusarium fujikuroi TOR kinase in nitrogen regulation and secondary metabolism.
abstract: In Fusarium fujikuroi, the biosynthesis of gibberellins (GAs) and bikaverin is under control of AreA-mediated nitrogen metabolite repression. Thus far, the signaling components acting upstream of AreA and regulating its nuclear translocation are unknown. In Saccharomyces cerevisiae, the target of rapamycin (TOR) proteins, Tor1p and Tor2p, are key players of nutrient-mediated signal transduction to control cell growth. In filamentous fungi, probably only one TOR kinase-encoding gene exists. However, nothing is known about its function. Therefore, we investigated the role of TOR in the GA-producing fungus F. fujikuroi in order to determine whether TOR plays a role in nitrogen regulation, especially in the regulation of GA and bikaverin biosynthesis. We cloned and characterized the F. fujikuroi tor gene. However, we were not able to create knockout mutants, suggesting that TOR is essential for viability. Inhibition of TOR by rapamycin affected the expression of AreA-controlled secondary metabolite genes for GA and bikaverin biosynthesis, as well as genes involved in transcriptional and translational regulation, ribosome biogenesis, and autophagy. Deletion of fpr1 encoding the FKBP12-homologue confirmed that the effects of rapamycin are due to the specific inhibition of TOR. Interestingly, the expression of most of the TOR target genes has been previously shown to be also affected in the glutamine synthetase mutant, although in the opposite way. We demonstrate here for the first time in a filamentous fungus that the TOR kinase is involved in nitrogen regulation of secondary metabolism and that rapamycin affects also the expression of genes involved in translation control, ribosome biogenesis, carbon metabolism, and autophagy.
authors.affiliation: Westfälische Wilhelms-Universität Münster, Institut für Botanik, Schlossgarten 3, D-48149 Münster, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Teichert
authors.forename: Marieke
authors.initials: M
authors.lastname: Wottawa
authors.forename: Birgit
authors.initials: B
authors.lastname: Schönig
authors.forename: Bettina
authors.initials: B
authors.lastname: Tudzynski
mesh_terms: D003001:Cloning, Molecular; D015536:Down-Regulation / Q000235:genetics; D020224:Expressed Sequence Tags; D005670:Fusarium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D020043:Genes, Essential / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics; D005822:Genetic Vectors; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009584:Nitrogen / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017422:Sequence Analysis, DNA; D020123:Sirolimus / Q000494:pharmacology; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D009584:Nitrogen; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020123:Sirolimus; D022061:Tacrolimus Binding Protein 1A