• KdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans.

      Gacek-Matthews, Agnieszka; Berger, Harald; Sasaki, Takahiko; Wittstein, Kathrin; Gruber, Clemens; Lewis, Zachary A; Strauss, Joseph; Helmholtzzentrum für Infektionsforschung, Inhoffenstrasse 7, 38124 Braunschweig (2016-08)
      Histone posttranslational modifications (HPTMs) are involved in chromatin-based regulation of fungal secondary metabolite biosynthesis (SMB) in which the corresponding genes-usually physically linked in co-regulated clusters-are silenced under optimal physiological conditions (nutrient-rich) but are activated when nutrients are limiting. The exact molecular mechanisms by which HPTMs influence silencing and activation, however, are still to be better understood. Here we show by a combined approach of quantitative mass spectrometry (LC-MS/MS), genome-wide chromatin immunoprecipitation (ChIP-seq) and transcriptional network analysis (RNA-seq) that the core regions of silent A. nidulans SM clusters generally carry low levels of all tested chromatin modifications and that heterochromatic marks flank most of these SM clusters. During secondary metabolism, histone marks typically associated with transcriptional activity such as H3 trimethylated at lysine-4 (H3K4me3) are established in some, but not all gene clusters even upon full activation. KdmB, a Jarid1-family histone H3 lysine demethylase predicted to comprise a BRIGHT domain, a zinc-finger and two PHD domains in addition to the catalytic Jumonji domain, targets and demethylates H3K4me3 in vivo and mediates transcriptional downregulation. Deletion of kdmB leads to increased transcription of about ~1750 genes across nutrient-rich (primary metabolism) and nutrient-limiting (secondary metabolism) conditions. Unexpectedly, an equally high number of genes exhibited reduced expression in the kdmB deletion strain and notably, this group was significantly enriched for genes with known or predicted functions in secondary metabolite biosynthesis. Taken together, this study extends our general knowledge about multi-domain KDM5 histone demethylases and provides new details on the chromatin-level regulation of fungal secondary metabolite production.
    • Kenalactams A-E, Polyene Macrolactams Isolated from Nocardiopsis CG3.

      Messaoudi, Omar; Sudarman, Enge; Bendahou, Mourad; Jansen, Rolf; Stadler, Marc; Wink, Joachim; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (American Cemical Society (ACS), 2019-05-24)
      In our screening program for new biologically active secondary metabolites, a new strain, Nocardiopsis CG3 (DSM 106572), isolated from the saltpan of Kenadsa, was found to produce five new polyene macrolactams, the kenalactams A-E (1-5). Their structures were elucidated by spectral methods (NMR and HRESIMS), and the absolute configuration was derived by chemical derivatization (Mosher's method). Through a feeding experiment, alanine was proven to be the nitrogen-bearing starter unit involved in biosynthesis of the polyketide kenalactam A (1). Kenalactam E (5) was cytotoxic against human prostate cancer PC-3 cells with an IC50 value of 2.1 μM.
    • Labyrinthopeptins as virolytic inhibitors of respiratory syncytial virus cell entry.

      Blockus, Sebastian; Sake, Svenja M; Wetzke, Martin; Grethe, Christina; Graalmann, Theresa; Pils, Marina; Le Goffic, Ronan; Galloux, Marie; Prochnow, Hans; Rox, Katharina; et al. (Elsevier, 2020-03-18)
      Acute lower respiratory tract infections (ALRI) caused by respiratory syncytial virus (RSV) are associated with a severe disease burden among infants and elderly patients. Treatment options are limited. While numerous drug candidates with different viral targets are under development, the utility of RSV entry inhibitors is challenged by a low resistance barrier and by single mutations causing cross-resistance against a wide spectrum of fusion inhibitor chemotypes. We developed a cell-based screening assay for discovery of compounds inhibiting infection with primary RSV isolates. Using this system, we identified labyrinthopeptin A1 and A2 (Laby A1/A2), lantibiotics isolated from Actinomadura namibiensis, as effective RSV cell entry inhibitors with IC50s of 0.39 μM and 4.97 μM, respectively, and with favourable therapeutic index (>200 and > 20, respectively). Both molecules were active against multiple RSV strains including primary isolates and their antiviral activity against RSV was confirmed in primary human airway cells ex vivo and a murine model in vivo. Laby A1/A2 were antiviral in prophylactic and therapeutic treatment regimens and displayed synergistic activity when applied in combination with each other. Mechanistic studies showed that Laby A1/A2 exert virolytic activity likely by binding to phosphatidylethanolamine moieties within the viral membrane and by disrupting virus particle membrane integrity. Probably due to its specific mode of action, Laby A1/A2 antiviral activity was not affected by common resistance mutations to known RSV entry inhibitors. Taken together, Laby A1/A2 represent promising candidates for development as RSV inhibitors. Moreover, the cell-based screening system with primary RSV isolates described here should be useful to identify further antiviral agents.
    • Labyrinthopeptins exert broad-spectrum antiviral activity through lipid-binding-mediated virolysis.

      Prochnow, Hans; Rox, Katharina; Birudukota, N V Suryanarayana; Weichert, Loreen; Hotop, Sven-Kevin; Klahn, Philipp; Mohr, Kathrin; Franz, Sergej; Banda, Dominic H; Blockus, Sebastian; et al. (ASM, 2019-10-30)
      To counteract the serious health threat posed by known and novel viral pathogens, drugs that target a variety of viruses through a common mechanism have attracted recent attention due to their potential in treating (re-)emerging infections, for which direct acting antivirals are not available. We found that labyrinthopeptins A1 and A2, the prototype congeners of carbacyclic lanthipeptides, inhibit the proliferation of diverse enveloped viruses, including Dengue virus, Zika virus, West Nile virus, Hepatitis C virus, Chikungunya virus, Karposi's Sarcoma-associated Herpes virus, Cytomegalovirus, and Herpes Simplex virus, in the low μM to nM range. Mechanistic studies on viral particles revealed that labyrinthopeptins induce a virolytic effect through binding to the viral membrane lipid phosphatidylethanolamine (PE). These effects are enhanced by a combined equimolar application of both labyrinthopeptins, and a clear synergism was observed across a concentration range corresponding to IC10-IC90 values of the compounds. Time-resolved experiments with large unilamellar vesicles (LUVs) reveal that membrane lipid raft compositions (PC/PE/Chol/SM (17:10:33:40)) are particularly sensitive to labyrinthopeptins compared to PC/PE (90:10) LUVs, even though the overall PE-amount remains constant. Labyrinthopeptins exhibited low cytotoxicity and had favorable pharmacokinetic properties in mice (t1/2= 10.0 h), which designates them as promising antiviral compounds acting by an unusual viral lipid targeting mechanism.Importance For many viral infections, current treatment options are insufficient. Because the development of each antiviral drug is time-consuming and expensive, the prospect of finding broad-spectrum antivirals that can fight multiple, diverse viruses - well-known as well as (re-)emerging species - has gained attention, especially for the treatment of viral co-infections. While most known broad spectrum agents address processes in the host cell, we found that targeting lipids of the free virus outside the host cell with the natural products labyrinthopeptin A1 and A2 is a viable strategy to inhibit the proliferation of a broad range of viruses from different families, including Chikungunya virus, Dengue virus, Zika virus, Karposi's Sarcoma-associated Herpes virus, or Cytomegalovirus. Labyrinthopeptins bind to viral phosphatidylethanolamine and induce virolysis without exerting cytotoxicity to host cells. This represents a novel and unusual mechanism to tackle medically relevant viral infections.
    • Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

      Mulwa, Lucky S.; Jansen, Rolf; Praditya, Dimas F.; Mohr, Kathrin I.; Okanya, Patrick W.; Wink, Joachim; Steinmann, Eike; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Beilstein-Institut, 2018-06-26)
      Lanyamycin (1/2), a secondary metabolite occurring as two epimers, was isolated from the myxobacterium Sorangium cellulosum, strain Soce 481. The structures of both epimers were elucidated from HRESIMS and 1D and 2D NMR data and the relative configuration of their macrolactone ring was assigned based on NOE and vicinal 1H NMR coupling constants and by calculation of a 3D model. Lanyamycin inhibited HCV infection into mammalian liver cells with an IC50 value of 11.8 µM, and exhibited a moderate cytotoxic activity against the mouse fibroblast cell line L929 and the human nasopharyngeal cell line KB3 with IC50 values of 3.1 and 1.5 μM, respectively, and also suppressed the growth of the Gram-positive bacterium Micrococcus luteus.
    • Large Scale Production and Downstream Processing of Labyrinthopeptins from the Actinobacterium .

      Rupcic, Zeljka; Hüttel, Stephan; Bernecker, Steffen; Kanaki, Sae; Stadler, Marc; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-06-05)
      A method was established for the production of 1.2-fold and 4.2-fold increased amounts of the antiviral and central nervous system-active lantipeptides, labyrinthopeptins A1 and A2, respectively, isolated from the actinobacterium
    • Lentinulactam, a hirsutane sesquiterpene with an unprecedented lactam modification

      Helaly, Soleiman E.; Richter, Christian; Thongbai, Benjarong; Hyde, Kevin D.; Stadler, Marc; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016-12)
    • Litoralimycins A and B, New Cytotoxic Thiopeptides from Streptomonospora sp. M2.

      Khodamoradi, Shadi; Stadler, Marc; Wink, Joachim; Surup, Frank; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2020-05-26)
      Streptomonospora sp. M2 has been isolated from a soil sample collected at the Wadden Sea beach in our ongoing program aimed at the isolation of rare Actinobacteria, ultimately targeting the discovery of new antibiotics. Because crude extracts derived from cultures of this strain showed inhibitory activity against the indicator organism Bacillus subtilis, it was selected for further analysis. HPLC-MS analysis of its culture broth revealed the presence of lipophilic metabolites. The two major metabolites of those were isolated by preparative reversed-phase HPLC and preparative TLC. Their planar structures were elucidated using high-resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D NMR data as new thiopeptide antibiotics and named litoralimycin A (1) and B (2). Although rotating frame nuclear Overhauser effect spectroscopy (ROESY) data established a Z configuration of the Δ21,26 double bond, the stereochemistry of C-5 and C-15 were assigned as S by Marfey's method after ozonolysis. The biological activity spectrum of 1 and 2 is highly uncommon for thiopeptide antibiotics, since they showed only insignificant antibacterial activity, but 1 showed strong cytotoxic effects.
    • Macrooxazoles A-D, New 2,5-Disubstituted Oxazole-4-Carboxylic Acid Derivatives from the Plant Pathogenic Fungus .

      Matio Kemkuignou, Blondelle; Treiber, Laura; Zeng, Haoxuan; Schrey, Hedda; Schobert, Rainer; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2020-11-24)
      In our ongoing search for new bioactive fungal metabolites, four previously undescribed oxazole carboxylic acid derivatives (1-4) for which we proposed the trivial names macrooxazoles A-D together with two known tetramic acids (5-6) were isolated from the plant pathogenic fungus Phoma macrostoma. Their structures were elucidated based on high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. The hitherto unclear structure of macrocidin Z (6) was also confirmed by its first total synthesis. The isolated compounds were evaluated for their antimicrobial activities against a panel of bacteria and fungi. Cytotoxic and anti-biofilm activities of the isolates are also reported herein. The new compound 3 exhibited weak-to-moderate antimicrobial activity as well as the known macrocidins 5 and 6. Only the mixture of compounds 2 and 4 (ratio 1:2) showed weak cytotoxic activity against the tested cancer cell lines with an IC50 of 23 µg/mL. Moreover, the new compounds 2 and 3, as well as the known compounds 5 and 6, interfered with the biofilm formation of Staphylococcus aureus, inhibiting 65%, 75%, 79%, and 76% of biofilm at 250 µg/mL, respectively. Compounds 5 and 6 also exhibited moderate activity against S. aureus preformed biofilm with the highest inhibition percentage of 75% and 73% at 250 µg/mL, respectively.
    • Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology.

      Nazir, Mamona; Saleem, Muhammad; Tousif, Muhammad Imran; Anwar, Muhammad Aijaz; Surup, Frank; Ali, Iftikhar; Wang, Daijie; Mamadalieva, Nilufar Z; Alshammari, Elham; Ashour, Mohamed L; et al. (MDPI, 2021-06-29)
      Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.
    • Microfungi associated with Clematis (Ranunculaceae) with an integrated approach to delimiting species boundaries

      Phukhamsakda, Chayanard; McKenzie, Eric H. C.; Phillips, Alan J. L.; Gareth Jones, E. B.; Jayarama Bhat, D.; Stadler, Marc; Bhunjun, Chitrabhanu S.; Wanasinghe, Dhanushka N.; Thongbai, Benjarong; Camporesi, Erio; et al. (Springer Science and Business Media LLC, 2020-07-07)
      The cosmopolitan plant genus Clematis contains many climbing species that can be found worldwide. The genus occurs in the wild and is grown commercially for horticulture. Microfungi on Clematis were collected from Belgium, China, Italy, Thailand and the UK. They are characterized by morphology and analyses of gene sequence data using an integrated species concept to validate identifications. The study revealed two new families, 12 new genera, 50 new species, 26 new host records with one dimorphic character report, and ten species are transferred to other genera. The new families revealed by multigene phylogeny are Longiostiolaceae and Pseudomassarinaceae in Pleosporales (Dothideomycetes). New genera are Anthodidymella (Didymellaceae), Anthosulcatispora and Parasulcatispora (Sulcatisporaceae), Fusiformispora (Amniculicolaceae), Longispora (Phaeosphaeriaceae), Neobyssosphaeria (Melanommataceae), Neoleptosporella (Chaetosphaeriales, genera incertae sedis), Neostictis (Stictidaceae), Pseudohelminthosporium (Neomassarinaceae), Pseudomassarina (Pseudomassarinaceae), Sclerenchymomyces (Leptosphaeriaceae) and Xenoplectosphaerella (Plectosphaerellaceae). The newly described species are Alloleptosphaeria clematidis, Anthodidymella ranunculacearum, Anthosulcatispora subglobosa, Aquadictyospora clematidis, Brunneofusispora clematidis, Chaetosphaeronema clematidicola, C. clematidis, Chromolaenicola clematidis, Diaporthe clematidina, Dictyocheirospora clematidis, Distoseptispora clematidis, Floricola clematidis, Fusiformispora clematidis, Hermatomyces clematidis, Leptospora clematidis, Longispora clematidis, Massariosphaeria clematidis, Melomastia clematidis, M. fulvicomae, Neobyssosphaeria clematidis, Neoleptosporella clematidis, Neoroussoella clematidis, N. fulvicomae, Neostictis nigricans, Neovaginatispora clematidis, Parasulcatispora clematidis, Parathyridaria clematidis, P. serratifoliae, P. virginianae, Periconia verrucose, Phomatospora uniseriata, Pleopunctum clematidis, Pseudocapulatispora clematidis, Pseudocoleophoma clematidis, Pseudohelminthosporium clematidis, Pseudolophiostoma chiangraiense, P. clematidis, Pseudomassarina clematidis, Ramusculicola clematidis, Sarocladium clematidis, Sclerenchymomyces clematidis, Sigarispora clematidicola, S. clematidis, S. montanae, Sordaria clematidis, Stemphylium clematidis, Wojnowiciella clematidis, Xenodidymella clematidis, Xenomassariosphaeria clematidis and Xenoplectosphaerella clematidis. The following fungi are recorded on Clematis species for the first time: Angustimassarina rosarum, Dendryphion europaeum, Dermatiopleospora mariae, Diaporthe ravennica, D. rudis, Dichotomopilus ramosissimum, Dictyocheirospora xishuangbannaensis, Didymosphaeria rubi-ulmifolii, Fitzroyomyces cyperacearum, Fusarium celtidicola, Leptospora thailandica, Memnoniella oblongispora, Neodidymelliopsis longicolla, Neoeutypella baoshanensis, Neoroussoella heveae, Nigrograna chromolaenae, N. obliqua, Pestalotiopsis verruculosa, Pseudoberkleasmium chiangmaiense, Pseudoophiobolus rosae, Pseudoroussoella chromolaenae, P. elaeicola, Ramusculicola thailandica, Stemphylium vesicarium and Torula chromolaenae. The new combinations are Anthodidymella clematidis (≡ Didymella clematidis), A. vitalbina (≡ Didymella vitalbina), Anthosulcatispora brunnea (≡ Neobambusicola brunnea), Fuscohypha kunmingensis (≡ Plectosphaerella kunmingensis), Magnibotryascoma rubriostiolata (≡ Teichospora rubriostiolata), Pararoussoella mangrovei (≡ Roussoella mangrovei), Pseudoneoconiothyrium euonymi (≡ Roussoella euonymi), Sclerenchymomyces jonesii (≡ Neoleptosphaeria jonesii), Stemphylium rosae (≡ Pleospora rosae), and S. rosae-caninae (≡ Pleospora rosae-caninae). The microfungi on Clematis is distributed in several classes of Ascomycota. The analyses are based on morphological examination of specimens, coupled with phylogenetic sequence data. To the best of our knowledge, the consolidated species concept approach is recommended in validating species.
    • A microfungus from Costa Rica: <I>Ticosynnema</I> gen. nov.

      Castañeda-Ruiz, Rafael F.; Granados, María M.; Mardones, Melissa; Stadler, Marc; Minter, David W.; Hernández-Restrepo, Margarita; Gené, Josepa; Guarro, Josep (2014-06-10)
    • Mimonoside D: a new triterpenoid saponin from Sauvalle (Fabaceae).

      Kenmogne, Claudie Fokou; Ponou, Beaudelaire Kemvoufo; Kemkuignou, Blondelle Matio; Kühlborn, Jonas; Tchuenguem, Roland T; Teponno, Rémy Bertrand; Dzoyem, Jean Paul; Opatz, Till; Tapondjou, Léon Azefack; BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany. (Taylor & Francis, 2021-11-29)
      A new triterpenoid saponin (Mimonoside D: 3-O-α-L-arabinopyranosyl-3β-hydroxyolean-12-en-28-oic acid 28-O-β-D-xylopyranosyl-(1→2)-β-D- glucopyranoside ester (1)) was isolated from the aerial parts of Mimosa diplotricha Sauvalle together with nine known compounds: 7,4'-dihydroxyflavone (2), kaempferol (3), lupeol (4), betulinic acid (5), β-sitosterol (6), β-sitosterol-3-O-β-D-glucopyranoside (7), lutein (8), 5,2'-dihydroxy-7,4',5'-trimethoxyflavone (9) and vitexin (10). Their structures were elucidated on the basis of spectroscopic (1 D and 2 D nuclear magnetic resonance) and high-resolution mass spectrometric data as well as by comparison of their spectral data with those of related compounds. Compounds 2, 7 and 8 had already been isolated from M. diplotricha, while compounds 3, 4, 5 and 6 have been isolated from other Mimosa species. Compound 2 moderately inhibited Proteus mirabilis (MIC = 32 µg/mL), weakly inhibited Pseudomonas aeruginosa (MIC = 64 µg/mL) and very weakly inhibited Staphylococcus aureus (MIC = 128 µg/mL) and Enterococus faecalis (MIC = 128 µg/mL).
    • Minimizing the chaos following the loss of Article 59: Suggestions for a discussion

      Gams, Walter; Humber, Richard A.; Jaklitsch, Walter; Kirschner, Roland; Stadler, Marc (2012-07-03)
    • Minutellins A - D, azaphilones from the stromata of Annulohypoxylon minutellum (Xylariaceae).

      Kuhnert, Eric; Surup, Frank; Halecker, Sandra; Stadler, Marc; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-02-16)
      During the course of our screening for new metabolites with chemotaxonomic importance from stromata of fungi from the family Xylariaceae, we characterized several interesting metabolites in the fungus Annulohypoxylon minutellum. Extraction of the fruiting bodies and purification by preparative HPLC resulted in the isolation of five metabolites. The main compound was identified as the known metabolite hinnulin A (5), while four minor compounds were found to represent previously undescribed azaphilones, named minutellins A - D (1-4). Their planar structures were elucidated using NMR and HRESIMS data; absolute stereochemistry was assigned by CD data and Mosher's method. Compounds 1, 3 and 5 showed cytotoxic effects against murine and human cells. As the production of 1-5 is restricted to a group of closely related Annulohypoxylon species, they serve well as chemotaxonomic marker.
    • Modular synthesis of polyene side chain analogues of the potent macrolide antibiotic etnangien by a flexible coupling strategy based on hetero-bis-metallated alkenes.

      Altendorfer, Mario; Raja, Aruna; Sasse, Florenz; Irschik, Herbert; Menche, Dirk; University of Heidelberg, Department of Organic Chemistry, INF 270, D-69120 Heidelberg, Germany, EU. (2013-04-07)
      An efficient procedure for the concise synthesis of hetero-bis-metallated alkenes as useful building blocks for the modular access to highly elaborate polyenes and stabilized analogues is reported. By applying these bifunctional olefins in convergent Stille/Suzuki-Miyaura couplings, novel, carefully selected side chain analogues of the potent RNA polymerase inhibitor etnangien were synthesized by a modular late stage coupling strategy and evaluated for antibacterial and antiproliferative activities.
    • Molecular Phylogeny and Morphology of (=Lepteutypa ) (Amphisphaeriaceae).

      Samarakoon, Milan C; Maharachchikumbura, Sajeewa S N; Liu, Jian-Kui Jack; Hyde, Kevin D; Promputtha, Itthayakorn; Stadler, Marc; HZI, Helmholtz Zentrum für Infektionsforschung, GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (MDPI, 2020-09-17)
      Amphisphaeriaceous taxa (fungi) are saprobes on decaying wood in terrestrial, mangrove, and freshwater habitats. The generic boundaries of the family have traditionally been based on morphology, and the delimitation of genera has always been challenging. Amphisphaeria species have clypeate ascomata and 1-septate ascospores and a coelomycetous asexual morph. Lepteutypa is different from Amphisphaeria in having eutypoid stromata and more than 1-septate ascospores. These main characters have been used for segregation of Lepteutypa from Amphisphaeria for a long time. However, the above characters are overlapping among Amphisphaeria and Lepteutypa species. Therefore, here we synonymized Lepteutypa under Amphisphaeria based on holomorphic morphology and multigene phylogeny. Further, our cluster analysis reveals the relationship between seven morphological traits among Amphisphaeria/Lepteutypa species and suggests those morphologies are not specific to either genus. Three new species (i.e., Amphisphaeria camelliae, A. curvaticonidia, and A. micheliae) are introduced based on morphology and LSU-ITS-RPB2-TUB2 phylogenies. Furthermore, the monotypic genus Trochilispora, which had been accepted in Amphisphaeriaceae, is revisited and synonymized under Hymenopleella and placed in Sporocadaceae.
    • Monochlorinated calocerins A-D and 9-oxostrobilurin derivatives from the basidiomycete Favolaschia calocera.

      Chepkirui, Clara; Richter, Christian; Matasyoh, Josphat Clement; Stadler, Marc; Helmholtz Centre for infection research, Ihoffenstr. 7, 38124 Braunschweig, Germany. (2016-12)
      Eight previously undescribed compounds were isolated and characterised from the supernatant and mycelium of a culture of the basidiomycete Favolaschia calocera originating from Kakamega equatorial rainforest in Kenya. These were: 9- oxostrobilurins A, G, K and I and the four monochlorinated calocerins A, B, C and D. The calocerins extend our knowledge of halogenated compounds obtained from natural sources. Four further known compounds were also identified: strobilurin G, favolon, pterulinic acid and 2,3 -dihydro-1-benzoxepin derivative. The four oxostrobilurins exhibited prominent antifungal and cytotoxic activities while the four calocerins only showed cytotoxic activity.
    • Monocillium gamsii sp. nov. and Monocillium bulbillosum: two nematode-associated fungi parasitising the eggs of Heterodera filipjevi

      Ashrafi, Samad; Stadler, Marc; Dababat, Abdelfattah A.; Richert-Pöggeler, Katja R.; Finckh, Maria R.; Maier, Wolfgang; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany. (2017-10-25)
    • A "Motif-Oriented" Total Synthesis of Nannocystin Ax. Preparation and Biological Assessment of Analogues.

      Meng, Zhanchao; Souillart, Laetitia; Monks, Brendan; Huwyler, Nikolas; Herrmann, Jennifer; Müller, Rolf; Fürstner, Alois; HIPS, Helmholtz-Institut füt Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (2018-07-06)
      The highly cytotoxic cyclodepsipeptides of the nannocystin family are known to bind to the eukaryotic translation elongation factor 1α (EF-1α). Analysis of the docking pose, as proposed by a previous in silico study, suggested that the trisubstituted alkene moiety and the neighboring methyl ether form a domain that might be closely correlated with biological activity. This hypothesis sponsored a synthetic campaign which was designed to be "motif-oriented": specifically, a sequence of ring closing alkyne metathesis (RCAM) followed by hydroxy-directed trans-hydrostannation of the resulting cycloalkyne was conceived, which allowed this potentially anchoring substructure to be systematically addressed at a late stage. This inherently flexible approach opened access to nannocystin Ax (1) itself as well as to 10 non-natural analogues. While the biological data confirmed the remarkable potency of this class of compounds and showed that the domain in question is indeed an innate part of the pharmacophore, the specific structure/activity relationships can only partly be reconciled with the original in silico docking study; therefore, we conclude that this model needs to be carefully revisited.