Light-dependent coordination of development and secondary metabolism in the filamentous fungus Aspergillus nidulans
Final Report Abstract
Fungal development is affected by external signals including light, which promotes in Aspergillus nidulans enhanced asexual spore formation to disperse asexual conidia into the air. Darkness and a low oxygen to carbon dioxide ratio promote sexual development resulting in closed sexual fruiting bodies as resting structures in the soil with sexual ascospores. Asexual and sexual development are linked to the production of distinct and different secondary metabolites, which are also affected by the presence of other organisms in the environment. Hülle cells are a specific Aspergillus cell type of specialized multinuclear cells, which nurse and protect the sexual fruiting bodies of Aspergillus nidulans. The fungal-specific velvet domain proteins coordinate development to the appropriate secondary metabolism. Velvet domain proteins can form homo- and heterodimers with different functions in development and are monitored by the cellular protein stability control. In the last funding period we have shown, that velvet factor controlled Hülle cells of A. nidulans with nuclear storage and developmental backup functions are reminiscent of multipotent stem cells. We have identified various secondary metabolites of Hülle cells, which require the velvet regulators for their synthesis. These metabolites mediate protection of fungal reproductive and overwintering structures against fungivorous animals. As response to the presence of glycopetide-producing Streptomycetes bacteria, A. nidulans produces antibacterial ironchelating tropolones. Nuclear F-box proteins control substrate stability and subcellular location of regulatory proteins to organize fungal development and to anticipate stress. F-box proteins are receptors of the cell to label proteins for degradation by the 26S proteasome. The exchange of F-box receptors of SCFs requires the COP9 signalosome. Fungal COP9 signalosome assembly requires connection of two trimeric intermediates for integration of intrinsic deneddylase activity. A molecular circuit between A. nidulans transcription factors MsnA and VelB coordinates fungal stress and developmental responses. Induction of Aspergillus fumigatus zinc cluster transcription factor OdrA/Mdu2 provides combined cellular responses for oxidative stress protection and multiple antifungal drug tolerances.
Publications
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Hülle Cells of Aspergillus nidulans with Nuclear Storage and Developmental Backup Functions Are Reminiscent of Multipotent Stem Cells. mBio, 11(4).
Troppens, Danielle M.; Köhler, Anna M.; Schlüter, Rabea; Hoppert, Michael; Gerke, Jennifer & Braus, Gerhard H.
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The High Osmolarity Glycerol Mitogen-Activated Protein Kinase regulates glucose catabolite repression in filamentous fungi. PLOS Genetics, 16(8), e1008996.
de Assis, Leandro José; Silva, Lilian Pereira; Liu, Li; Schmitt, Kerstin; Valerius, Oliver; Braus, Gerhard H.; Ries, Laure Nicolas Annick & Goldman, Gustavo Henrique
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Draft Genome Sequence of Saccharomyces cerevisiae LW2591Y, a Laboratory Strain for In Vivo Multigene Assemblies. Microbiology Resource Announcements, 10(9).
Gerke, Jennifer; Schneider, Dominik; Poehlein, Anja; Cornish, Virginia W. & Braus, Gerhard H.
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Secondary metabolites of Hülle cells mediate protection of fungal reproductive and overwintering structures against fungivorous animals. eLife, 10.
Liu, Li; Sasse, Christoph; Dirnberger, Benedict; Valerius, Oliver; Fekete-Szücs, Enikő; Harting, Rebekka; Nordzieke, Daniela E.; Pöggeler, Stefanie; Karlovsky, Petr; Gerke, Jennifer & Braus, Gerhard H.
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Biosynthesis of Antibacterial Iron-Chelating Tropolones in Aspergillus nidulans as Response to Glycopeptide-Producing Streptomycetes. Frontiers in Fungal Biology, 2.
Gerke, Jennifer; Köhler, Anna M.; Wennrich, Jan-Peer; Große, Verena; Shao, Lulu; Heinrich, Antje K.; Bode, Helge B.; Chen, Wanping; Surup, Frank & Braus, Gerhard H.
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F-box receptor mediated control of substrate stability and subcellular location organizes cellular development of Aspergillus nidulans. PLOS Genetics, 18(12), e1010502.
Sarikaya, Bayram Özlem; Bayram, Özgür; Karahoda, Betim; Meister, Cindy; Köhler, Anna M.; Thieme, Sabine; Elramli, Nadia; Frawley, Dean; McGowan, Jamie; Fitzpatrick, David A.; Schmitt, Kerstin; de Assis, Leandro Jose; Valerius, Oliver; Goldman, Gustavo H. & Braus, Gerhard H.
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Fungal COP9 signalosome assembly requires connection of two trimeric intermediates for integration of intrinsic deneddylase. Proceedings of the National Academy of Sciences, 120(35).
Bakti, Fruzsina; Stupperich, Helena; Schmitt, Kerstin; Valerius, Oliver; Köhler, Anna M.; Meister, Cindy; Strohdiek, Anja; Harting, Rebekka; Sasse, Christoph; Heimel, Kai; Neumann, Piotr; Ficner, Ralf & Braus, Gerhard H.
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Induction of Aspergillus fumigatus zinc cluster transcription factor OdrA/Mdu2 provides combined cellular responses for oxidative stress protection and multiple antifungal drug resistance. mBio, 14(6).
Sasse, Christoph; Bastakis, Emmanouil; Bakti, Fruzsina; Höfer, Annalena M.; Zangl, Isabella; Schüller, Christoph; Köhler, Anna M.; Gerke, Jennifer; Krappmann, Sven; Finkernagel, Florian; Harting, Rebekka; Strauss, Joseph; Heimel, Kai & Braus, Gerhard H.
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Molecular circuit between Aspergillus nidulans transcription factors MsnA and VelB to coordinate fungal stress and developmental responses. openRxiv.
Bastakis, Emmanouil; Gerke, Jennifer; Özkan, Seyma; Harting, Rebekka; Lienard, Tanja; Sasse, Christoph; Xylakis, Emmanouil S.; Aden, Merle; Strohdiek, Anja; Heinrich, Gabriele; Grosse, Verena & Braus, Gerhard H.
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The Aspergillus nidulans velvet domain containing transcription factor VeA is shuttled from cytoplasm into nucleus during vegetative growth and stays there for sexual development, but has to return into cytoplasm for asexual development. openRxiv.
Strohdiek, Anja; Köhler, Anna M.; Harting, Rebekka; Stupperich, Helena; Gerke, Jennifer; Bastakis, Emmanouil; Neumann, Piotr; Ahmed, Yasar L.; Ficner, Ralf & Braus, Gerhard H.
