• The Effect of Cytochalasans on the Actin Cytoskeleton of Eukaryotic Cells and Preliminary Structure⁻Activity Relationships.

      Kretz, Robin; Wendt, Lucile; Wongkanoun, Sarunyou; Luangsa-Ard, J Jennifer; Surup, Frank; Helaly, Soleiman E; Noumeur, Sara R; Stadler, Marc; Stradal, Theresia E B; HZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig Germany. (MDPI, 2019-02-19)
      In our ongoing search for new bioactive fungal metabolites, two new cytochalasans were isolated from stromata of the hypoxylaceous ascomycete Hypoxylon fragiforme. Their structures were elucidated via high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. Together with 23 additional cytochalasans isolated from ascomata and mycelial cultures of different Ascomycota, they were tested on their ability to disrupt the actin cytoskeleton of mammal cells in a preliminary structure–activity relationship study. Out of all structural features, the presence of hydroxyl group at the C7 and C18 residues, as well as their stereochemistry, were determined as important factors affecting the potential to disrupt the actin cytoskeleton. Moreover, reversibility of the actin disrupting effects was tested, revealing no direct correlations between potency and reversibility in the tested compound group. Since the diverse bioactivity of cytochalasans is interesting for various applications in eukaryotes, the exact effect on eukaryotic cells will need to be determined, e.g., by follow-up studies involving medicinal chemistry and by inclusion of additional natural cytochalasans. The results are also discussed in relation to previous studies in the literature, including a recent report on the anti-Biofilm activities of essentially the same panel of compounds against the pathogenic bacterium, Staphylococcus aureus. View Full-Text
    • Structures of an RNA polymerase promoter melting intermediate elucidate DNA unwinding.

      Boyaci, Hande; Chen, James; Jansen, Rolf; Darst, Seth A; Campbell, Elizabeth A; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Nature publishing group, 2019-01-09)
      A key regulated step of transcription is promoter melting by RNA polymerase (RNAP) to form the open promoter complex
    • An endothelial cell line infected by Kaposi's sarcoma-associated herpes virus (KSHV) allows the investigation of Kaposi's sarcoma and the validation of novel viral inhibitors in vitro and in vivo.

      Dubich, Tatyana; Lieske, Anna; Santag, Susann; Beauclair, Guillaume; Rückert, Jessica; Herrmann, Jennifer; Gorges, Jan; Büsche, Guntram; Kazmaier, Uli; Hauser, Hansjörg; Stadler, Marc; Schulz, Thomas F; Wirth, Dagmar; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2019-01-04)
      Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), a tumor of endothelial origin predominantly affecting immunosuppressed individuals. Up to date, vaccines and targeted therapies are not available. Screening and identification of anti-viral compounds are compromised by the lack of scalable cell culture systems reflecting properties of virus-transformed cells in patients. Further, the strict specificity of the virus for humans limits the development of in vivo models. In this study, we exploited a conditionally immortalized human endothelial cell line for establishment of in vitro 2D and 3D KSHV latency models and the generation of KS-like xenograft tumors in mice. Importantly, the invasive properties and tumor formation could be completely reverted by purging KSHV from the cells, confirming that tumor formation is dependent on the continued presence of KSHV, rather than being a consequence of irreversible transformation of the infected cells. Upon testing a library of 260 natural metabolites, we selected the compounds that induced viral loss or reduced the invasiveness of infected cells in 2D and 3D endothelial cell culture systems. The efficacy of selected compounds against KSHV-induced tumor formation was verified in the xenograft model. Together, this study shows that the combined use of anti-viral and anti-tumor assays based on the same cell line is predictive for tumor reduction in vivo and therefore allows faithful selection of novel drug candidates against Kaposi's sarcoma. KEY MESSAGES: Novel 2D, 3D, and xenograft mouse models mimic the consequences of KSHV infection. KSHV-induced tumorigenesis can be reverted upon purging the cells from the virus. A 3D invasiveness assay is predictive for tumor reduction in vivo. Chondramid B, epothilone B, and pretubulysin D diminish KS-like lesions in vivo.
    • Bacillus methylotrophicus ASWU-C2, a strain inhabiting hot desert soil, a new source for antibacterial bacillopyrone, pyrophen, and cyclopeptides

      Helaly, Soleiman E.; Hamad, Zainab; El Sayed, Magdi A.; Abdel-Motaal, Fatma F.; Nassar, Mahmoud I.; Ito, Shin-ichi; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Walter de Gruyter, 2018-12-14)
    • Cytochalasans Act as Inhibitors of Biofilm Formation of Staphylococcus Aureus.

      Yuyama, Kamila Tomoko; Wendt, Lucile; Surup, Frank; Kretz, Robin; Chepkirui, Clara; Wittstein, Kathrin; Boonlarppradab, Chollaratt; Wongkanoun, Sarunyou; Luangsa-Ard, Jennifer; Stadler, Marc; Abraham, Wolf-Rainer; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2018-10-30)
      During the course of our ongoing work to discover new inhibitors of biofilm formation of Staphylococcus aureus from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete Hypoxylon fragiforme for the first time. Two new compounds were purified by a bioassay-guided fractionation procedure; their structures were elucidated subsequently by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). This unexpected finding prompted us to test further cytochalasans from other fungi and from commercial sources for comparison. Out of 21 cytochalasans, 13 showed significant inhibition of Staphylococcus aureus biofilm formation at subtoxic levels. These findings indicate the potential of cytochalasans as biofilm inhibitors for the first time, also because the minimum inhibitory concentrations (MIC) are independent of the anti-biofilm activities. However, cytochalasans are known to be inhibitors of actin, making some of them very toxic for eukaryotic cells. Since the chemical structures of the tested compounds were rather diverse, the inclusion of additional derivatives, as well as the evaluation of their selectivity against mammalian cells vs. the bacterium, will be necessary as next step in order to develop structure-activity relationships and identify the optimal candidates for development of an anti-biofilm agent. View Full-Text
    • Antiviral 4-Hydroxypleurogrisein and Antimicrobial Pleurotin Derivatives from Cultures of the Nematophagous Basidiomycete .

      Sandargo, Birthe; Thongbai, Benjarong; Praditya, Dimas; Steinmann, Eike; Stadler, Marc; Surup, Frank; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany; TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany. (2018-10-19)
      4-Hydroxypleurogrisein, a congener of the anticancer-lead compound pleurotin, as well as six further derivatives were isolated from the basidiomycete Hohenbuehelia grisea, strain MFLUCC 12-0451. The structures were elucidated utilizing high resolution electron spray ionization mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR) spectral data and evaluated for their biological activities; for leucopleurotin, we provide Xray data. While most congeners showed moderate antimicrobial and cytotoxic activity, 4-hydroxypleurogrisein emerged as an inhibitor of hepatitis C virus infectivity in mammalian liver cells.
    • Biofilm Inhibitory Abscisic Acid Derivatives from the Plant-Associated Dothideomycete Fungus, sp.

      Phukhamsakda, Chayanard; Macabeo, Allan Patrick G; Yuyama, Kamila Tomoko; Hyde, Kevin David; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2018-08-30)
      Roussoella species are well recorded from both monocotyledons and dicotyledons. As part of a research program to discover biologically active compounds from plant-associated Dothideomycetes in Thailand, the strain Roussoella sp. (MFLUCC 17-2059), which represents an undescribed species, was isolated from Clematis subumbellata Kurz, fermented in yeast-malt medium and explored for its secondary metabolite production. Bioassay-guided fractionation of the crude extract yielded the new abscisic acid derivative, roussoellenic acid (1), along with pestabacillin B (2), a related congener, and the cyclodipeptide, cyclo(S-Pro-S-Ile) (3). The structure of 1 was determined by 2D NMR spectroscopy and HR-ESIMS data analysis. Compounds 1 and 2 showed inhibitory activity on biofilm formation by Staphylococcus aureus. The biofilm formation of S. aureus was reduced to 34% at 16 µg/mL by roussoellenic acid (1), while pestabacillin B (2) only showed 36% inhibition at 256 µg/mL. In addition, compound 1 also had weak cytotoxic effects on L929 murine fibroblasts and human KB3-1 cancer cells.
    • 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
    • Considerations and consequences of allowing DNA sequence data as types of fungal taxa.

      Zamora, Juan Carlos; Svensson, Måns; Kirschner, Roland; Olariaga, Ibai; Ryman, Svengunnar; Parra, Luis Alberto; Geml, József; Rosling, Anna; Adamčík, Slavomír; Ahti, Teuvo; Aime, M Catherine; Ainsworth, A Martyn; Albert, László; Albertó, Edgardo; García, Alberto Altés; Ageev, Dmitry; Agerer, Reinhard; Aguirre-Hudson, Begoña; Ammirati, Joe; Andersson, Harry; Angelini, Claudio; Antonín, Vladimír; Aoki, Takayuki; Aptroot, André; Argaud, Didier; Sosa, Blanca Imelda Arguello; Aronsen, Arne; Arup, Ulf; Asgari, Bita; Assyov, Boris; Atienza, Violeta; Bandini, Ditte; Baptista-Ferreira, João Luís; Baral, Hans-Otto; Baroni, Tim; Barreto, Robert Weingart; Beker, Henry; Bell, Ann; Bellanger, Jean-Michel; Bellù, Francesco; Bemmann, Martin; Bendiksby, Mika; Bendiksen, Egil; Bendiksen, Katriina; Benedek, Lajos; Bérešová-Guttová, Anna; Berger, Franz; Berndt, Reinhard; Bernicchia, Annarosa; Biketova, Alona Yu; Bizio, Enrico; Bjork, Curtis; Boekhout, Teun; Boertmann, David; Böhning, Tanja; Boittin, Florent; Boluda, Carlos G; Boomsluiter, Menno W; Borovička, Jan; Brandrud, Tor Erik; Braun, Uwe; Brodo, Irwin; Bulyonkova, Tatiana; Burdsall, Harold H; Buyck, Bart; Burgaz, Ana Rosa; Calatayud, Vicent; Callac, Philippe; Campo, Emanuele; Candusso, Massimo; Capoen, Brigitte; Carbó, Joaquim; Carbone, Matteo; Castañeda-Ruiz, Rafael F; Castellano, Michael A; Chen, Jie; Clerc, Philippe; Consiglio, Giovanni; Corriol, Gilles; Courtecuisse, Régis; Crespo, Ana; Cripps, Cathy; Crous, Pedro W; da Silva, Gladstone Alves; da Silva, Meiriele; Dam, Marjo; Dam, Nico; Dämmrich, Frank; Das, Kanad; Davies, Linda; De Crop, Eske; De Kesel, Andre; De Lange, Ruben; De Madrignac Bonzi, Bárbara; Dela Cruz, Thomas Edison E; Delgat, Lynn; Demoulin, Vincent; Desjardin, Dennis E; Diederich, Paul; Dima, Bálint; Dios, Maria Martha; Divakar, Pradeep Kumar; Douanla-Meli, Clovis; Douglas, Brian; Drechsler-Santos, Elisandro Ricardo; Dyer, Paul S; Eberhardt, Ursula; Ertz, Damien; Esteve-Raventós, Fernando; Salazar, Javier Angel Etayo; Evenson, Vera; Eyssartier, Guillaume; Farkas, Edit; Favre, Alain; Fedosova, Anna G; Filippa, Mario; Finy, Péter; Flakus, Adam; Fos, Simón; Fournier, Jacques; Fraiture, André; Franchi, Paolo; Molano, Ana Esperanza Franco; Friebes, Gernot; Frisch, Andreas; Fryday, Alan; Furci, Giuliana; Márquez, Ricardo Galán; Garbelotto, Matteo; García-Martín, Joaquina María; Otálora, Mónica A García; Sánchez, Dania García; Gardiennet, Alain; Garnica, Sigisfredo; Benavent, Isaac Garrido; Gates, Genevieve; da Cruz Lima Gerlach, Alice; Ghobad-Nejhad, Masoomeh; Gibertoni, Tatiana B; Grebenc, Tine; Greilhuber, Irmgard; Grishkan, Bella; Groenewald, Johannes Z; Grube, Martin; Gruhn, Gérald; Gueidan, Cécile; Gulden, Gro; Gusmão, Luis Fp; Hafellner, Josef; Hairaud, Michel; Halama, Marek; Hallenberg, Nils; Halling, Roy E; Hansen, Karen; Harder, Christoffer Bugge; Heilmann-Clausen, Jacob; Helleman, Stip; Henriot, Alain; Hernandez-Restrepo, Margarita; Herve, Raphaël; Hobart, Caroline; Hoffmeister, Mascha; Høiland, Klaus; Holec, Jan; Holien, Håkon; Hughes, Karen; Hubka, Vit; Huhtinen, Seppo; Ivančević, Boris; Jagers, Marian; Jaklitsch, Walter; Jansen, AnnaElise; Jayawardena, Ruvishika S; Jeppesen, Thomas Stjernegaard; Jeppson, Mikael; Johnston, Peter; Jørgensen, Per Magnus; Kärnefelt, Ingvar; Kalinina, Liudmila B; Kantvilas, Gintaras; Karadelev, Mitko; Kasuya, Taiga; Kautmanová, Ivona; Kerrigan, Richard W; Kirchmair, Martin; Kiyashko, Anna; Knapp, Dániel G; Knudsen, Henning; Knudsen, Kerry; Knutsson, Tommy; Kolařík, Miroslav; Kõljalg, Urmas; Košuthová, Alica; Koszka, Attila; Kotiranta, Heikki; Kotkova, Vera; Koukol, Ondřej; Kout, Jiří; Kovács, Gábor M; Kříž, Martin; Kruys, Åsa; Kučera, Viktor; Kudzma, Linas; Kuhar, Francisco; Kukwa, Martin; Arun Kumar, T K; Kunca, Vladimír; Kušan, Ivana; Kuyper, Thomas W; Lado, Carlos; Læssøe, Thomas; Lainé, Patrice; Langer, Ewald; Larsson, Ellen; Larsson, Karl-Henrik; Laursen, Gary; Lechat, Christian; Lee, Serena; Lendemer, James C; Levin, Laura; Lindemann, Uwe; Lindström, Håkan; Liu, Xingzhong; Hernandez, Regulo Carlos Llarena; Llop, Esteve; Locsmándi, Csaba; Lodge, Deborah Jean; Loizides, Michael; Lőkös, László; Luangsa-Ard, Jennifer; Lüderitz, Matthias; Lumbsch, Thorsten; Lutz, Matthias; Mahoney, Dan; Malysheva, Ekaterina; Malysheva, Vera; Manimohan, Patinjareveettil; Marin-Felix, Yasmina; Marques, Guilhermina; Martínez-Gil, Rubén; Marson, Guy; Mata, Gerardo; Matheny, P Brandon; Mathiassen, Geir Harald; Matočec, Neven; Mayrhofer, Helmut; Mehrabi, Mehdi; Melo, Ireneia; Mešić, Armin; Methven, Andrew S; Miettinen, Otto; Romero, Ana M Millanes; Miller, Andrew N; Mitchell, James K; Moberg, Roland; Moreau, Pierre-Arthur; Moreno, Gabriel; Morozova, Olga; Morte, Asunción; Muggia, Lucia; González, Guillermo Muñoz; Myllys, Leena; Nagy, István; Nagy, László G; Neves, Maria Alice; Niemelä, Tuomo; Nimis, Pier Luigi; Niveiro, Nicolas; Noordeloos, Machiel E; Nordin, Anders; Noumeur, Sara Raouia; Novozhilov, Yuri; Nuytinck, Jorinde; Ohenoja, Esteri; Fiuza, Patricia Oliveira; Orange, Alan; Ordynets, Alexander; Ortiz-Santana, Beatriz; Pacheco, Leticia; Pál-Fám, Ferenc; Palacio, Melissa; Palice, Zdeněk; Papp, Viktor; Pärtel, Kadri; Pawlowska, Julia; Paz, Aurelia; Peintner, Ursula; Pennycook, Shaun; Pereira, Olinto Liparini; Daniëls, Pablo Pérez; Pérez-De-Gregorio Capella, Miquel À; Del Amo, Carlos Manuel Pérez; Gorjón, Sergio Pérez; Pérez-Ortega, Sergio; Pérez-Vargas, Israel; Perry, Brian A; Petersen, Jens H; Petersen, Ronald H; Pfister, Donald H; Phukhamsakda, Chayanard; Piątek, Marcin; Piepenbring, Meike; Pino-Bodas, Raquel; Esquivel, Juan Pablo Pinzón; Pirot, Paul; Popov, Eugene S; Popoff, Orlando; Álvaro, María Prieto; Printzen, Christian; Psurtseva, Nadezhda; Purahong, Witoon; Quijada, Luis; Rambold, Gerhard; Ramírez, Natalia A; Raja, Huzefa; Raspé, Olivier; Raymundo, Tania; Réblová, Martina; Rebriev, Yury A; de Dios Reyes García, Juan; Ripoll, Miguel Ángel Ribes; Richard, Franck; Richardson, Mike J; Rico, Víctor J; Robledo, Gerardo Lucio; Barbosa, Flavia Rodrigues; Rodriguez-Caycedo, Cristina; Rodriguez-Flakus, Pamela; Ronikier, Anna; Casas, Luis Rubio; Rusevska, Katerina; Saar, Günter; Saar, Irja; Salcedo, Isabel; Martínez, Sergio M Salcedo; Montoya, Carlos A Salvador; Sánchez-Ramírez, Santiago; Sandoval-Sierra, J Vladimir; Santamaria, Sergi; Monteiro, Josiane Santana; Schroers, Hans Josef; Schulz, Barbara; Schmidt-Stohn, Geert; Schumacher, Trond; Senn-Irlet, Beatrice; Ševčíková, Hana; Shchepin, Oleg; Shirouzu, Takashi; Shiryaev, Anton; Siepe, Klaus; Sir, Esteban B; Sohrabi, Mohammad; Soop, Karl; Spirin, Viacheslav; Spribille, Toby; Stadler, Marc; Stalpers, Joost; Stenroos, Soili; Suija, Ave; Sunhede, Stellan; Svantesson, Sten; Svensson, Sigvard; Svetasheva, Tatyana Yu; Świerkosz, Krzysztof; Tamm, Heidi; Taskin, Hatira; Taudière, Adrien; Tedebrand, Jan-Olof; Lahoz, Raúl Tena; Temina, Marina; Thell, Arne; Thines, Marco; Thor, Göran; Thüs, Holger; Tibell, Leif; Tibell, Sanja; Timdal, Einar; Tkalčec, Zdenko; Tønsberg, Tor; Trichies, Gérard; Triebel, Dagmar; Tsurykau, Andrei; Tulloss, Rodham E; Tuovinen, Veera; Sosa, Miguel Ulloa; Urcelay, Carlos; Valade, François; Garza, Ricardo Valenzuela; van den Boom, Pieter; Van Vooren, Nicolas; Vasco-Palacios, Aida M; Vauras, Jukka; Velasco Santos, Juan Manuel; Vellinga, Else; Verbeken, Annemieke; Vetlesen, Per; Vizzini, Alfredo; Voglmayr, Hermann; Volobuev, Sergey; von Brackel, Wolfgang; Voronina, Elena; Walther, Grit; Watling, Roy; Weber, Evi; Wedin, Mats; Weholt, Øyvind; Westberg, Martin; Yurchenko, Eugene; Zehnálek, Petr; Zhang, Huang; Zhurbenko, Mikhail P; Ekman, Stefan (2018-06-01)
      Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
    • Screening for inhibitors of mutacin synthesis in Streptococcus mutans using fluorescent reporter strains.

      Premnath, Priyanka; Reck, Michael; Wittstein, Kathrin; Stadler, Marc; Wagner-Döbler, Irene; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (BMC, 2018-03-27)
      Within the polymicrobial dental plaque biofilm, bacteria kill competitors by excreting mixtures of bacteriocins, resulting in improved fitness and survival. Inhibiting their bacteriocin synthesis might therefore be a useful strategy to eliminate specific pathogens. We used Streptococcus mutans, a highly acidogenic inhabitant of dental plaque, as a model and searched for natural products that reduced mutacin synthesis. To this end we fused the promoter of mutacin VI to the GFP+ gene and integrated the construct into the genome of S. mutans UA159 by single homologous recombination. The resulting reporter strain 423p - gfp + was used to screen 297 secondary metabolites from different sources, mainly myxobacteria and fungi, for their ability to reduce the fluorescence of the fully induced reporter strain by > 50% while growth was almost unaffected (> 90% of control). Seven compounds with different chemical structures and different modes of action were identified. Erinacine C was subsequently validated and shown to inhibit transcription of all three mutacins of S. mutans. The areas of the inhibition zones of the sensor strains S. sanguinis and Lactococcus lactis were reduced by 35% to 61% in comparison to controls in the presence of erinacine C, demonstrating that the amount of active mutacins in the culture supernatants of S. mutans was reduced. Erinacines are cyathane diterpenes that were extracted from cultures of the edible mushroom Hericium erinaceus. They have anti-inflammatory, antimicrobial and neuroprotective effects. For erinacine C, a new biological activity was found here. We demonstrate the successful development of a whole-cell fluorescent reporter for the screening of natural compounds and report that erinacine C suppresses mutacin synthesis in S. mutans without affecting cell viability.
    • Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum.

      Rupcic, Zeljka; Rascher, Monique; Kanaki, Sae; Köster, Reinhard W; Stadler, Marc; Wittstein, Kathrin; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-03-06)
      Basidiomycetes of the genusHericiumare among the most praised medicinal and edible mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor (NGF) or (as established more recently) brain-derived neurotrophic factor (BDNF) in cell-based bioassays. The present study reports on the metabolite profiles of a Lion's Mane mushroom (Hericium erinaceus) strain and a strain of the rare species,Hericium flagellum(synonymH. alpestre). While we observed highly similar metabolite profiles between the two strains that were examined, we isolated two previously undescribed metabolites, given the trivial names erinacines Z1 and Z2. Their chemical structures were elucidated by means of nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry. Along with six further, previously identified cyathane diterpenes, the novel erinacines were tested for neurotrophin inducing effects. We found that erinacines act onBDNF, which is a neurotrophic factor that has been reported recently by us to be induced by the corallocins, but as well onNGFexpression, which is consistent with the literature.
    • Novel and interesting Ophiocordyceps spp. ( Ophiocordycipitaceae , Hypocreales ) with superficial perithecia from Thailand

      Luangsa-ard, J.; Tasanathai, K.; Thanakitpipattana, D.; Khonsanit, A.; Stadler, M.; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-03)
    • Six Heterocyclic Metabolites from the Myxobacterium Labilithrix luteola.

      Mulwa, Lucky S; Jansen, Rolf; Praditya, Dimas F; Mohr, Kathrin I; Wink, Joachim; Steinmann, Eike; Stadler, Marc; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-02-28)
      Two new secondary metabolites, labindole A [2-methyl-3-(2-nitroethyl)-3H-indole] (1) and labindole B [2-methyl-3-(2-nitrovinyl)-3H-indole] (2), were isolated from the myxobacteriumLabilithrixluteola(DSM 27648T). Additionally, four metabolites3,4,5and6already known from other sources were obtained. Their structures were elucidated from high resolution electrospray ionisation mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR) spectroscopy data and their relative configuration was assigned based on nuclear Overhauser effect (NOE) and vicinal ¹H-NMR coupling data. The compounds where tested for biological activities; labindoles A (1) and B (2) exhibited significant activity against Hepatitis C Virus, 9H-carbazole (3), 3-chloro-9H-carbazole (4) and 4-hydroxymethyl-quinoline (5) showed antifungal activities. Moreover, compound3had weak to moderate antibacterial activities, while labindoles A (1) and B (2) were devoid of significant antifungal and antibacterial effects.
    • Aethiopinolones A-E, New Pregnenolone Type Steroids from the East African Basidiomycete Fomitiporia aethiopica.

      Chepkirui, Clara; Sum, Winnie C; Cheng, Tian; Matasyoh, Josphat C; Decock, Cony; Stadler, Marc; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-02-09)
      A mycelial culture of the Kenyan basidiomyceteFomitiporia aethiopicawas fermented on rice and the cultures were extracted with methanol. Subsequent HPLC profiling and preparative chromatography of its crude extract led to the isolation of five previously undescribed pregnenolone type triterpenes1-5, for which we propose the trivial name aethiopinolones A-E. The chemical structures of the aethiopinolones were determined by extensive 1D- and 2D-NMR, and HRMS data analysis. The compounds exhibited moderate cytotoxic effects against various human cancer cell lines, but they were found devoid of significant nematicidal and antimicrobial activities.
    • Elsinopirins A-D, Decalin Polyketides from the Ascomycete Elsinoё pyri.

      Surup, Frank; Pommerehne, Kathrin; Schroers, Hans-Josef; Stadler, Marc; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-02-05)
      In course of our screening for new secondary metabolites from ecological niche specialized, phytopathogenic fungi, the plant pathogenElsinoё pyri, strain 2203C, was found to produce four novel compounds (1-4), which were named elsinopirins A-D, in addition to the known metabolite elsinochrome A (5). After isolation by preparative high-performance liquid chromatography (HPLC), their structures, including relative stereochemistry, were elucidated by 1D and 2D nuclear magnetic resonance (NMR) and mass spectrometry (MS) data. Finally, absolute stereochemistry was assigned by chemical shifts of Mosher's esters (α-methoxy-α-trifluoromethylphenylacetic acid; MTPA) derivatives of elsinopirin B (2). The compounds were found to be devoid of significant antibacterial, antifungal, and cytotoxic activities.
    • Acetyl-CoA carboxylase 1 regulates endothelial cell migration by shifting the phospholipid composition.

      Glatzel, Daniel K; Koeberle, Andreas; Pein, Helmut; Löser, Konstantin; Stark, Anna; Keksel, Nelli; Werz, Oliver; Müller, Rolf; Bischoff, Iris; Fürst, Robert; HIPS, Helmholtz-Institute für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany. (2018-02)
      The enzyme acetyl-CoA carboxylase (ACC) plays a crucial role in fatty acid metabolism. In recent years, ACC has been recognized as a promising drug target for treating different diseases. However, the role of ACC in vascular endothelial cells (ECs) has been neglected so far. To characterize the role of ACC, we used the ACC inhibitor, soraphen A, as a chemical tool, and also a gene silencing approach. We found that ACC1 was the predominant isoform in human umbilical vein ECs as well as in human microvascular ECs and that soraphen A reduced the levels of malonyl-CoA. We revealed that ACC inhibition shifted the lipid composition of EC membranes. Accordingly, membrane fluidity, filopodia formation, and migratory capacity were reduced. The antimigratory action of soraphen A depended on an increase in the cellular proportion of PUFAs and, most importantly, on a decreased level of phosphatidylglycerol. Our study provides a causal link between ACC, membrane lipid composition, and cell migration in ECs. Soraphen A represents a useful chemical tool to investigate the role of fatty acid metabolism in ECs and ACC inhibition offers a new and valuable therapeutic perspective for the treatment of EC migration-related diseases.
    • Two novel species of (Parabambusicolaceae, Pleosporales) with their phoma-like asexual morphs.

      Phukhamsakda, Chayanard; Bhat, Darbhe J; Hongsanan, Sinang; Xu, Jian-Chu; Stadler, Marc; Hyde, Kevin D; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-01-01)
      The monotypic genus
    • New nematicidal and antimicrobial secondary metabolites from a new species in the new genus, .

      Rupcic, Zeljka; Chepkirui, Clara; Hernández-Restrepo, Margarita; Crous, Pedro W; Luangsa-Ard, Janet Jennifer; Stadler, Marc; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-01-01)
      During the course of a study on the functional biodiversity of the mycobiota inhabiting rainforests in Thailand, a fungal strain was isolated from a plant sample and shown to represent an undescribed species, as inferred from a combination of morphological and molecular phylogenetic methods. Molecular phylogenetic analyses, based on four DNA loci, revealed a phylogenetic tree with the newly generated sequences clustering in a separate branch, together with members of the Sulcatisporaceae (Pleosporales, Ascomycota). The Thai specimen morphologically resembled
    • New nematicidal and antimicrobial secondary metabolites from a new species in the new genus, .

      Rupcic, Zeljka; Chepkirui, Clara; Hernández-Restrepo, Margarita; Crous, Pedro W; Luangsa-Ard, Janet Jennifer; Stadler, Marc; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-01-01)
      During the course of a study on the functional biodiversity of the mycobiota inhabiting rainforests in Thailand, a fungal strain was isolated from a plant sample and shown to represent an undescribed species, as inferred from a combination of morphological and molecular phylogenetic methods. Molecular phylogenetic analyses, based on four DNA loci, revealed a phylogenetic tree with the newly generated sequences clustering in a separate branch, together with members of the Sulcatisporaceae (Pleosporales, Ascomycota). The Thai specimen morphologically resembled
    • Volatiles from the hypoxylaceous fungi and Hypoxylon macrocarpum.

      Rinkel, Jan; Babczyk, Alexander; Wang, Tao; Stadler, Marc; Dickschat, Jeroen S; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2018-01-01)
      The volatiles emitted by the ascomycetes