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Minou Nowrousian - One of the best experts on this subject based on the ideXlab platform.
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Sordaria macrospora : 25 years as a model organism for studying the molecular mechanisms of fruiting body development
Applied microbiology and biotechnology, 2020Co-Authors: Ines Teichert, Stefanie Pöggeler, Minou NowrousianAbstract:Fruiting bodies are among the most complex multicellular structures formed by fungi, and the molecular mechanisms that regulate their development are far from understood. However, studies with a number of fungal model organisms have started to shed light on this developmental process. One of these model organisms is Sordaria macrospora, a filamentous ascomycete from the order Sordariales. This fungus has been a genetic model organism since the 1950s, but its career as a model organism for molecular genetics really took off in the 1990s, when the establishment of a transformation protocol, a mutant collection, and an indexed cosmid library provided the methods and resources to start revealing the molecular mechanisms of fruiting body development. In the 2000s, "omics" methods were added to the S. macrospora tool box, and by 2020, 58 developmental genes have been identified in this fungus. This review gives a brief overview of major method developments for S. macrospora, and then focuses on recent results characterizing different processes involved in regulating development including several regulatory protein complexes, autophagy, transcriptional and chromatin regulation, and RNA editing. KEY POINTS: •Sordaria macrospora is a model system for analyzing fungal fruiting body development. •More than 100 developmental mutants are available for S. macrospora. •More than 50 developmental genes have been characterized in S. macrospora.
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Additional file 18: of The transcription factor PRO44 and the histone chaperone ASF1 regulate distinct aspects of multicellular development in the filamentous fungus Sordaria macrospora
2018Co-Authors: David Immanuel Schumacher, Ines Teichert, Ramona LĂźtkenhaus, Florian Altegoer, Ulrich KĂźck, Minou NowrousianAbstract:Table S3. Sordaria macrospora strains used in this study. (PDF 288 kb
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Additional file 15: of The transcription factor PRO44 and the histone chaperone ASF1 regulate distinct aspects of multicellular development in the filamentous fungus Sordaria macrospora
2018Co-Authors: David Immanuel Schumacher, Ines Teichert, Ramona LĂźtkenhaus, Florian Altegoer, Ulrich KĂźck, Minou NowrousianAbstract:Figure S13. Multiple alignment of SMAC_09436 (ASM2) orthologs. Orthologs were determined by bidirectional BLASTP analyses. Proteins from the Sordariomycetes Sordaria macrospora (S.m., SMAC_09436), Neurospora crassa (N.c., NCU010258), Podospora anserina (P.a., CDP26737.1), Magnaporthe oryzae (M.o., XP_003720415.1), Fusarium graminearum (F.g., FGRAMPH1_01T14721), and Trichoderma reesei (T.r., XP_006961730.1) were aligned with ClustalX. No clear orthologs outside of the Sordariomycetes could be identified. The GAL4 (GAL4-like Zn2Cys6 binuclear cluster DNA-binding) domain and the fungal_TF_MHR (fungal transcription factor regulatory middle homology region) domain in SMAC_09436 are indicated by black and grey bars, respectively, above the sequence. (PDF 176 kb
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Sordaria macrospora, a Model System for Fungal Development
Physiology and Genetics, 2009Co-Authors: Ulrich Kuck, Minou Nowrousian, Stefanie Pöggeler, Nicole Nolting, Ines EnghAbstract:The homothallic ascomycete Sordaria macrospora has a long-standing history as a classic genetic model system for conventional tetrad analysis. Further, it serves as a model organism to investigate the formation of fruiting bodies that are generated during the sexual life cycle of this filamentous fungus. The application of several molecular tools, such as DNA-mediated transformation, site-specific recombination or functional genomics to this filamentous fungus makes it an ideal experimental system to uncover the details of multicellular development. The rapid and inexpensive genetic analysis of developmental mutants with distinct and defined morphological defects, together with fluorescence microscopy of recombinant strains carrying GPF-tagged developmental proteins should further unravel the spatio-temporal network of regulatory factors. The sum of these investigations will contribute to our understanding of multicellular differentiation processes in eukaryotic model organisms
Robert J. Capon - One of the best experts on this subject based on the ideXlab platform.
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talarolide a a cyclic heptapeptide hydroxamate from an australian marine tunicate associated fungus talaromyces sp cmb tu011
Organic Letters, 2017Co-Authors: Pradeep Dewapriya, Pritesh Prasad, Rakesh Damodar, Angela A. Salim, Robert J. CaponAbstract:A miniaturized 24-well plate microbioreactor approach was used to explore secondary metabolite media dependence in an Australian marine tunicate-associated fungus, Talaromyces sp. (CMB TU011). Detailed chemical investigations of an antifungal M1-saline cultivation yielded talarolide A (1), only the second reported natural cyclic peptide hydroxamate, and the first from a fungus. The antifungal properties of the M1-saline extract were attributed to the known diterpene glycoside Sordarin (2). Structure elucidation of 1 and 2 was achieved by detailed spectroscopic analysis, with amino acid configurations in 1 assigned by the C3 and C18 Marfey’s methods, and l-Ala and d-Ala regiochemistry by the recently reported 2D C3 Marfey’s method.
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Talarolide A, a Cyclic Heptapeptide Hydroxamate from an Australian Marine Tunicate-Associated Fungus, Talaromyces sp. (CMB-TU011)
2017Co-Authors: Pradeep Dewapriya, Pritesh Prasad, Rakesh Damodar, Angela A. Salim, Robert J. CaponAbstract:A miniaturized 24-well plate microbioreactor approach was used to explore secondary metabolite media dependence in an Australian marine tunicate-associated fungus, Talaromyces sp. (CMB TU011). Detailed chemical investigations of an antifungal M1-saline cultivation yielded talarolide A (1), only the second reported natural cyclic peptide hydroxamate, and the first from a fungus. The antifungal properties of the M1-saline extract were attributed to the known diterpene glycoside Sordarin (2). Structure elucidation of 1 and 2 was achieved by detailed spectroscopic analysis, with amino acid configurations in 1 assigned by the C3 and C18 Marfey’s methods, and l-Ala and d-Ala regiochemistry by the recently reported 2D C3 Marfey’s method
Maria G Gomezlorenzo - One of the best experts on this subject based on the ideXlab platform.
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domain movements of elongation factor eef2 and the eukaryotic 80s ribosome facilitate trna translocation
The EMBO Journal, 2004Co-Authors: Maria G Gomezlorenzo, Gregers R Andersen, Rene Jorgensen, Christian M T Spahn, Robert A Grassucci, Roland BeckmannAbstract:An 11.7-A-resolution cryo-EM map of the yeast 80S·eEF2 complex in the presence of the antibiotic Sordarin was interpreted in molecular terms, revealing large conformational changes within eEF2 and the 80S ribosome, including a rearrangement of the functionally important ribosomal intersubunit bridges. Sordarin positions domain III of eEF2 so that it can interact with the sarcin–ricin loop of 25S rRNA and protein rpS23 (S12p). This particular conformation explains the inhibitory action of Sordarin and suggests that eEF2 is stalled on the 80S ribosome in a conformation that has similarities with the GTPase activation state. A ratchet-like subunit rearrangement (RSR) occurs in the 80S·eEF2·Sordarin complex that, in contrast to Escherichia coli 70S ribosomes, is also present in vacant 80S ribosomes. A model is suggested, according to which the RSR is part of a mechanism for moving the tRNAs during the translocation reaction.
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three dimensional cryo electron microscopy localization of ef2 in the saccharomyces cerevisiae 80s ribosome at 17 5 a resolution
The EMBO Journal, 2000Co-Authors: Maria G Gomezlorenzo, Juan P G Ballesta, Christian M T Spahn, Robert A Grassucci, Jose Garciabustos, Rajendra K Agrawal, Pawel A Penczek, Kalpana Chakraburtty, Jose Luis Lavandera, Joachim FrankAbstract:Using a Sordarin derivative, an antifungal drug, it was possible to determine the structure of a eukaryotic ribosome·EF2 complex at 17.5 A resolution by three‐dimensional (3D) cryo‐electron microscopy. EF2 is directly visible in the 3D map and the overall arrangement of the complex from Saccharomyces cerevisiae corresponds to that previously seen in Escherichia coli . However, pronounced differences were found in two prominent regions. First, in the yeast system the interaction between the elongation factor and the stalk region of the large subunit is much more extensive. Secondly, domain IV of EF2 contains additional mass that appears to interact with the head of the 40S subunit and the region of the main bridge of the 60S subunit. The shape and position of domain IV of EF2 suggest that it might interact directly with P‐site‐bound tRNA.
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Sordarin inhibits fungal protein synthesis by blocking translocation differently to fusidic acid
Journal of Biological Chemistry, 1999Co-Authors: Juan Manuel Dominguez, Maria G Gomezlorenzo, Julio MartinAbstract:Sordarin derivatives are selective inhibitors of fungal protein synthesis, which specifically impair elongation factor 2 (EF-2) function. We have studied the effect of Sordarin on the ribosome-dependent GTPase activity of EF-2 fromCandida albicans in the absence of any other component of the translation system. The effect of Sordarin turned out to be dependent both on the ratio of ribosomes to EF-2 and on the nature of the ribosomes. When the amount of EF-2 exceeded that of ribosomes Sordarin inhibited the GTPase activity following an inverted bell-shaped dose-response curve, whereas when EF-2 and ribosomes were in equimolar concentrations Sordarin yielded a typical sigmoidal dose-dependent inhibition. However, when ricin-treated ribosomes were used, Sordarin stimulated the hydrolysis of GTP. These results were compared with those obtained with fusidic acid, showing that both drugs act in a different manner. All these data are consistent with Sordarin blocking the elongation cycle at the initial steps of translocation, prior to GTP hydrolysis. In agreement with this conclusion, Sordarin prevented the formation of peptidyl-[3H]puromycin on polysomes from Candida albicans.
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ribosomal p protein stalk function is targeted by Sordarin antifungals
Journal of Biological Chemistry, 1998Co-Authors: Maria G Gomezlorenzo, Jose GarciabustosAbstract:Sordarin derivatives are remarkably selective inhibitors of fungal protein synthesis. Available evidence points to a binding site for these inhibitors on elongation factor 2, but high affinity binding requires the presence of ribosomes. The gene mutated in one of the two isolated complementation groups of Saccharomyces cerevisiae mutants resistant to the Sordarin derivative GM193663 has now been identified. It is RPP0, encoding the essential protein of the large ribosomal subunit stalk rpP0. Resistant mutants are found to retain most of the binding capacity for the drug, indicating that mutations in rpP0 endow the ribosome with the capacity to perform translation elongation in the presence of the inhibitor. Other proteins of the ribosomal stalk influence the expression of resistance, pointing to a wealth of interactions between stalk components and elongation factors. The involvement of multiple elements of the translation machinery in the mode of action of Sordarin antifungals may explain the large selectivity of these compounds, even though the individual target components are highly conserved proteins.
Stefanie Pöggeler - One of the best experts on this subject based on the ideXlab platform.
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Sordaria macrospora : 25 years as a model organism for studying the molecular mechanisms of fruiting body development
Applied microbiology and biotechnology, 2020Co-Authors: Ines Teichert, Stefanie Pöggeler, Minou NowrousianAbstract:Fruiting bodies are among the most complex multicellular structures formed by fungi, and the molecular mechanisms that regulate their development are far from understood. However, studies with a number of fungal model organisms have started to shed light on this developmental process. One of these model organisms is Sordaria macrospora, a filamentous ascomycete from the order Sordariales. This fungus has been a genetic model organism since the 1950s, but its career as a model organism for molecular genetics really took off in the 1990s, when the establishment of a transformation protocol, a mutant collection, and an indexed cosmid library provided the methods and resources to start revealing the molecular mechanisms of fruiting body development. In the 2000s, "omics" methods were added to the S. macrospora tool box, and by 2020, 58 developmental genes have been identified in this fungus. This review gives a brief overview of major method developments for S. macrospora, and then focuses on recent results characterizing different processes involved in regulating development including several regulatory protein complexes, autophagy, transcriptional and chromatin regulation, and RNA editing. KEY POINTS: •Sordaria macrospora is a model system for analyzing fungal fruiting body development. •More than 100 developmental mutants are available for S. macrospora. •More than 50 developmental genes have been characterized in S. macrospora.
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Sordaria macrospora
2020Co-Authors: Teichert, Ines Dr. Rer. Nat.), Stefanie Pöggeler, Minou Dr.) NowrousianAbstract:Fruiting bodies are among the most complex multicellular structures formed by fungi, and the molecular mechanisms that regulate their development are far from understood. However, studies with a number of fungal model organisms have started to shed light on this developmental process. One of these model organisms is \(\textit {Sordaria macrospora}\), a filamentous ascomycete from the order \(\textit {Sordariales}\). This fungus has been a genetic model organism since the 1950s, but its career as a model organism for molecular genetics really took off in the 1990s, when the establishment of a transformation protocol, a mutant collection, and an indexed cosmid library provided the methods and resources to start revealing the molecular mechanisms of fruiting body development. In the 2000s, “omics” methods were added to the \(\textit {S. macrospora}\) tool box, and by 2020, 58 developmental genes have been identified in this fungus. This review gives a brief overview of major method developments for \(\textit {S. macrospora}\), and then focuses on recent results characterizing different processes involved in regulating development including several regulatory protein complexes, autophagy, transcriptional and chromatin regulation, and RNA editing
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Sordaria macrospora, a Model System for Fungal Development
Physiology and Genetics, 2009Co-Authors: Ulrich Kuck, Minou Nowrousian, Stefanie Pöggeler, Nicole Nolting, Ines EnghAbstract:The homothallic ascomycete Sordaria macrospora has a long-standing history as a classic genetic model system for conventional tetrad analysis. Further, it serves as a model organism to investigate the formation of fruiting bodies that are generated during the sexual life cycle of this filamentous fungus. The application of several molecular tools, such as DNA-mediated transformation, site-specific recombination or functional genomics to this filamentous fungus makes it an ideal experimental system to uncover the details of multicellular development. The rapid and inexpensive genetic analysis of developmental mutants with distinct and defined morphological defects, together with fluorescence microscopy of recombinant strains carrying GPF-tagged developmental proteins should further unravel the spatio-temporal network of regulatory factors. The sum of these investigations will contribute to our understanding of multicellular differentiation processes in eukaryotic model organisms
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Visualization of peroxisomes via SKL-tagged DsRed protein in Sordaria macrospora
Fungal Genetics Reports, 2008Co-Authors: Skander Elleuche, Stefanie PöggelerAbstract:We report the utilization of Discosoma sp. red fluorescent protein DsRed to visualize peroxisomes in the filamentous ascomycete Sordaria macrospora. To achieve labeling of peroxisomes, DsRed was fused to a serine-lysine-leucine tag (SKL). Expression of the DsRed-SKL fusion gene under the control of the Aspergillus nidulans gpd-promoter led to protein import of DsRed into peroxisomes. In this study, we describe our results concerning the construction as well as the application of vector pDsRed-SKL.
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Mating-type genes from the homothallic fungus Sordaria macrospora are functionally expressed in a heterothallic ascomycete
Genetics, 1997Co-Authors: Stefanie Pöggeler, Ulrich Kuck, Siegfried Risch, Heinz D. OsiewaczAbstract:Homokaryons from the homothallic ascomycte Sordaria macrospora are able to enter the sexual pathway and to form fertile fruiting bodies. To analyze the molecular basis of homothallism and to elucidate the role of mating-products during fruiting body development, we cloned and sequenced the entire S. macrospora mating-type locus. Comparison of the Sordaria mating-type locus with mating-type idiomorphs from the heterothallic ascomycetes Neurospora crassa and Podospora anserina revealed that sequences from both idiomorphs ( A/a and mat –/ mat +, respectively) are contiguous in S. macrospora . DNA sequencing of the S. macrospora mating-type region allowed the identification of four open reading frames (ORFs), which were termed Smt-a1, SmtA-1, SmtA-2 and SmtA-3 . While Smt-a1, SmtA-1 , and SmtA-2 show strong sequence similarities with the corresponding N. crassa mating-type ORFs, SmtA-3 has a chimeric character. It comprises sequences that are similar to the A and a mating-type idiomorph from N. crassa . To determine functionality of the S. macrospora mating-type genes, we show that all ORFs are transcriptionally expressed. Furthermore, we transformed the S. macrospora mating-type genes into mat – and mat + strains of the closely related heterothallic fungus P. anserina . The transformation experiments show that mating-type genes from S. macrospora induce fruiting body formation in P. anserina .
Pradeep Dewapriya - One of the best experts on this subject based on the ideXlab platform.
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talarolide a a cyclic heptapeptide hydroxamate from an australian marine tunicate associated fungus talaromyces sp cmb tu011
Organic Letters, 2017Co-Authors: Pradeep Dewapriya, Pritesh Prasad, Rakesh Damodar, Angela A. Salim, Robert J. CaponAbstract:A miniaturized 24-well plate microbioreactor approach was used to explore secondary metabolite media dependence in an Australian marine tunicate-associated fungus, Talaromyces sp. (CMB TU011). Detailed chemical investigations of an antifungal M1-saline cultivation yielded talarolide A (1), only the second reported natural cyclic peptide hydroxamate, and the first from a fungus. The antifungal properties of the M1-saline extract were attributed to the known diterpene glycoside Sordarin (2). Structure elucidation of 1 and 2 was achieved by detailed spectroscopic analysis, with amino acid configurations in 1 assigned by the C3 and C18 Marfey’s methods, and l-Ala and d-Ala regiochemistry by the recently reported 2D C3 Marfey’s method.
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Talarolide A, a Cyclic Heptapeptide Hydroxamate from an Australian Marine Tunicate-Associated Fungus, Talaromyces sp. (CMB-TU011)
2017Co-Authors: Pradeep Dewapriya, Pritesh Prasad, Rakesh Damodar, Angela A. Salim, Robert J. CaponAbstract:A miniaturized 24-well plate microbioreactor approach was used to explore secondary metabolite media dependence in an Australian marine tunicate-associated fungus, Talaromyces sp. (CMB TU011). Detailed chemical investigations of an antifungal M1-saline cultivation yielded talarolide A (1), only the second reported natural cyclic peptide hydroxamate, and the first from a fungus. The antifungal properties of the M1-saline extract were attributed to the known diterpene glycoside Sordarin (2). Structure elucidation of 1 and 2 was achieved by detailed spectroscopic analysis, with amino acid configurations in 1 assigned by the C3 and C18 Marfey’s methods, and l-Ala and d-Ala regiochemistry by the recently reported 2D C3 Marfey’s method