group leader: Prof. Stadler

Recent Submissions

  • Cytotoxic, anti-biofilm and antimicrobial polyketides from the plant associated fungus Chaetosphaeronema achilleae.

    Narmani, Abolfazl; Teponno, Rémy Bertrand; Helaly, Soleiman E; Arzanlou, Mahdi; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2019-10-23)
    From extracts of the plant associated fungus Chaetosphaeronema achilleae collected in Iran, a previously unreported isoindolinone named chaetosisoindolinone (1) and a previously undescribed indanone named chaetosindanone (2) were isolated in addition to five known metabolites, 2-(2-acetyl-3,5-dihydroxyphenyl) acetic acid (3), vulculic acid (4), 2-(2-acetyl-3-hydroxy-5-methoxyphenyl)acetic acid (5), curvulin (6), and curvulol (7). Their structures were elucidated on the basis of extensive spectroscopic analysis and high-resolution mass spectrometry. The isolated compounds were tested for their antimicrobial, anti-biofilm, and nematicidal activities. Compound 2 exhibited cytotoxicity against the human breast adenocarcinoma MCF-7 cells with an IC50 value of 1.5 μg/mL. Furthermore, compounds 4 and 7 almost completely inhibited biofilm formation in Staphylococcus aureus at 256 μg/mL. Weak antimicrobial activities were also observed for some of the isolated compounds against Mucor hiemalis, Rhodoturula glutinis, Chromobacterium violaceum, and Staphylococcus aureus.
  • Sparticolins A-G, Biologically Active Oxidized Spirodioxynaphthalene Derivatives from the Ascomycete Sparticola junci.

    Phukhamsakda, Chayanard; Macabeo, Allan Patrick G; Huch, Volker; Cheng, Tian; Hyde, Kevin D; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (American Society of Chemistry, 2019-10-25)
    To explore the chemical diversity of metabolites from new species of Dothideomycetes, the ex-type strain of Sparticola junci was investigated. Seven highly oxygenated and functionalized spirodioxynaphthalene natural products incorporating carboxyalkylidene-cyclopentanoid (1-4), carboxyl-functionalized oxabicyclo[3.3.0]octane (5-6), and annelated 2-cyclopentenone/δ-lactone (7) units, sparticolins A-G, were isolated from submerged cultures of the fungus. Their chemical structures including their relative (and absolute) configurations were established through spectroscopic and X-ray crystallographic analyses. Sparticolin B (2) exhibited inhibitory activity against the Gram-positive bacteria Bacillus subtilis, Micrococcus luteus, and Staphylococcus aureus, while sparticolin G (7) showed antifungal activities against Schizosaccharomyces pombe and Mucor hiemalis. All other sparticolins were only weakly active against S. aureus and also showed weak activities against the nematode Caenorhabditis elegans. Compounds 2 and 7 also showed moderate cytotoxic activities against seven mammalian cell lines.
  • Two xanthones and two rotameric (3⟶8) biflavonoids from the Cameroonian medicinal plant Allanblackia floribunda Oliv. (Guttiferae)

    Mountessou, Bel Youssouf G.; Tchamgoue, Joseph; Paul Dzoyem, Jean; Tchuenguem, Roland T.; Surup, Frank; Choudhary, Muhammad I.; Green, Ivan R.; Kouam, Simeon F.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier BV, 2018-12)
    Two xanthones, 2-(3-hydroxy-3,3-dimethyldihydroallyl)-dihydro-6-deoxyisojacareubin (1) and dihydro-6-deoxyjacareubin (2), and two 3 ⟶ 8 rotameric biflavonoids, (2R,3S)-volkensiflavone-7-O-β-acetylglucopyranoside (3) and (2S,3S)-morelloflavone-7-O-β-acetylglucopyranoside (4), together with fifteen known compounds, were isolated from a dichloromethane/methanol (1:1, v/v) extract of the bark of the plant Allanblackia floribunda. The structures of the new compounds were elucidated by NMR spectroscopy and mass spectroscopic techniques and those of the known ones were deduced by comparison with data reported in the literature. The isolated biflavonoids were obtained as mixtures of conformers exhibiting duplicate NMR signals in solution at 25 °C and their respective absolute configurations were assigned using circular dichroism spectroscopy. Selected isolated compounds were assessed for their antibacterial and antioxidant properties
  • Structurally diverse metabolites from the rare actinobacterium Saccharothrix xinjiangensis.

    Babadi, Zahra Khosravi; Sudarman, Enge; Ebrahimipour, Gholam Hossein; Primahana, Gian; Stadler, Marc; Wink, Joachim; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Japan Antibiotics Research Association, 2019-08-26)
    The bioassay-guided fractionation from cultures of the actinobacterium Saccharothrix xinjiangensis Act24Zk, collected from the Caspian Sea beach in Iran led to the isolation of three new compounds, caerulomycin M (1), saccharopyrone (2), and saccharonoic acid (3), together with the known compound, caerulomycin A (4). Their structures were elucidated from HR-ESIMS and 1D and 2D NMR data. Compound 2 displayed moderate cytotoxic activity against the human cervix carcinoma HeLa cells KB3.1 with an IC50 value of 5.4 µM.
  • Volatiles from the tropical ascomycete (Hypoxylaceae, Xylariales).

    Wang, Tao; Mohr, Kathrin I; Stadler, Marc; Dickschat, Jeroen S; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany (Beilstein Institut, 2018-01-01)
    The volatiles from the fungus Daldinia clavata were collected by use of a closed-loop stripping apparatus and analysed by GC-MS. A few compounds were readily identified by comparison of measured to library mass spectra and of retention indices to published data, while for other compounds a synthesis of references was required. For one of the main compounds, 5-hydroxy-4,6-dimethyloctan-3-one, the relative and absolute configuration was determined by synthesis of all eight stereoisomers and gas chromatographic analysis using a homochiral stationary phase. Another identified new natural product is 6-nonyl-2H-pyran-2-one. The antimicrobial and cytotoxic effects of the synthetic volatiles are also reported.
  • Observations on Texas hypoxylons, including two new Hypoxylon species and widespread environmental isolates of the H. croceum complex identified by a polyphasic approach

    Sir, Esteban B.; Becker, Kevin; Lambert, Christopher; Bills, Gerald F.; Kuhnert, Eric; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Taylor & Francis, 2019-01-01)
  • A novel species and a new combination of Daldinia from Ban Hua Thung community forest in the northern part of Thailand

    Wongkanoun, Sarunyou; Wendt, Lucile; Stadler, Marc; Luangsa-ard, Jennifer; Srikitikulchai, Prasert; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Springer, 2019-04-02)
    During a survey of Xylariales in northern Thailand, several specimens with affinities to the genus Daldinia were found and examined for morphological characters, secondary metabolites, and molecular phylogenetic traits. Aside from morphological and chemotaxonomic studies, a multi-locus phylogenetic analysis using internal transcribed spacers regions (ITS) and the large subunit (LSU) of the ribosomal DNA, the second largest subunit of the RNA polymerase (RPB2), and beta-tubulin (TUB2) genes was performed. Among the specimens was a new species and a new record of a species that had previously never been sequenced and studied for its anamorphic morphology. This species, previously described by Ju and Rogers as Hypoxylon kretzschmarioides based on a single record from Indonesia, showed secondary metabolite profiles reminiscent of those of the genus Daldinia and even clustered in the latter genus in the phylogenetic tree. Therefore, it is transferred to Daldinia as D. kretzschmarioides comb. nov. A second new species, D. subvernicosa sp. nov., was found to have a close relationship with D. vernicosa based on morphological and molecular evidence, but differs from D. vernicosa by long-stipitate asci with mostly subglobose ascospores, and the basal ascospores are often elongated.
  • Antifungal metabolites from marine-derived Streptomyces sp. AMA49 against Pyricularia oryzae

    Buatong, Jirayu; Rukachaisirikul, Vatcharin; Sangkanu, Suthinee; Surup, Frank; Phongpaichit, Souwalak; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Oriental Scientific Pub Co(according to Zezoc), 2019-01-01)
    Marine-derived actinobacteria are considered as potential sources of bioactive metabolites including antifungal substances. Fifteen out of 155 marine-derived actinobacteria exhibited strong antifungal activity against the rice blast fungus Pyricularia oryzae. Their extracts were further determined for minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC). Ethyl acetate extract from the strain AMA49 and its subfraction AMA49F1 strongly inhibited hyphal growth of various P. oryzae strains with MICs (8 to 16µg/ml) and MFCs (16 to 128µg/ml) comparable to propiconazole. Both extracts destroyed fungal membrane and organelles, completely inhibited conidial germination, appressorium formation, and were non-toxic to Galleria mellonella. High performance liquid chromatography/mass spectrometry identified oligomycin A and its derivatives as the active components of AMA49F1 besides several diketopiperazines. AMA49 was identified as a Streptomyces sp. based on morphological characteristics and 16S rDNA sequence analysis. The results suggest that the Streptomyces sp. strain AMA49 is a potential biocontrol agent against rice blast pathogen P. oryzae. This is the first report on the inhibitory effect of the marine-derived Streptomyces extract containing oligomycin A and its derivatives on mycelial growth, conidial germination and appressorium formation of P. oryzae.
  • The amazing potential of fungi: 50 ways we can exploit fungi industrially

    Hyde, Kevin D.; Xu, Jianchu; Rapior, Sylvie; Jeewon, Rajesh; Lumyong, Saisamorn; Niego, Allen Grace T.; Abeywickrama, Pranami D.; Aluthmuhandiram, Janith V.S.; Brahamanage, Rashika S.; Brooks, Siraprapa; et al. (Springer, 2019-07-31)
    Fungi are an understudied, biotechnologically valuable group of organisms. Due to the immense range of habitats that fungi inhabit, and the consequent need to compete against a diverse array of other fungi, bacteria, and animals, fungi have developed numerous survival mechanisms. The unique attributes of fungi thus herald great promise for their application in biotechnology and industry. Moreover, fungi can be grown with relative ease, making production at scale viable. The search for fungal biodiversity, and the construction of a living fungi collection, both have incredible economic potential in locating organisms with novel industrial uses that will lead to novel products. This manuscript reviews fifty ways in which fungi can potentially be utilized as biotechnology. We provide notes and examples for each potential exploitation and give examples from our own work and the work of other notable researchers. We also provide a flow chart that can be used to convince funding bodies of the importance of fungi for biotechnological research and as potential products. Fungi have provided the world with penicillin, lovastatin, and other globally significant medicines, and they remain an untapped resource with enormous industrial potential.
  • Current insights into fungal species diversity and perspective on naming the environmental DNA sequences of fungi

    Wu, Bing; Hussain, Muzammil; Zhang, Weiwei; Stadler, Marc; Liu, Xingzhong; Xiang, Meichun; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Taylor&Francis, 2019-07-03)
    The global bio-diversity of fungi has been extensively investigated and their species number has been estimated. Notably, the development of molecular phylogeny has revealed an unexpected fungal diversity and utilisation of culture-independent approaches including high-throughput amplicon sequencing has dramatically increased number of fungal operational taxonomic units. A number of novel taxa including new divisions, classes, orders and new families have been established in last decade. Many cryptic species were identified by molecular phylogeny. Based on recently generated data from culture-dependent and -independent survey on same samples, the fungal species on the earth were estimated to be 12 (11.7–13.2) million compared to 2.2–3.8 million species recently estimated by a variety of the estimation techniques. Moreover, it has been speculated that the current use of high-throughput sequencing techniques would reveal an even higher diversity than our current estimation. Recently, the formal classification of environmental sequences and permission of DNA sequence data as fungal names’ type were proposed but strongly objected by the mycologist community. Surveys on fungi in unusual niches have indicated that many previously regarded “unculturable fungi” could be cultured on certain substrates under specific conditions. Moreover, the high-throughput amplicon sequencing, shotgun metagenomics and a single-cell genomics could be a powerful means to detect novel taxa. Here, we propose to separate the fungal types into physical type based on specimen, genome DNA (gDNA) type based on complete genome sequence of culturable and uncluturable fungal specimen and digital type based on environmental DNA sequence data. The physical and gDNA type should have priority, while the digital type can be temporal supplementary before the physical type and gDNA type being available. The fungal name based on the “digital type” could be assigned as the “clade” name + species name. The “clade” name could be the name of genus, family or order, etc. which the sequence of digital type affiliates to. Facilitating future cultivation efforts should be encouraged. Also, with the advancement in knowledge of fungi inhabiting various environments mostly because of rapid development of new detection technologies, more information should be expected for fungal diversity on our planet. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
  • Cyathane Diterpenes from Cultures of the Bird's Nest Fungus Cyathus hookeri and Their Neurotrophic and Anti-neuroinflammatory Activities.

    Tang, Dan; Xu, Yuan-Zhen; Wang, Wei-Wei; Yang, Zhi; Liu, Bo; Stadler, Marc; Liu, Ling-Li; Gao, Jin-Ming; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (American Chemical Society, 2019-06-18)
    Six new cyathane diterpenoids, cyahookerins A-F (1-6), as well as nine known analogues (7-15), were isolated from the liquid culture of the basidiomycete Cyathus hookeri. Their structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, HRESIMS, and ECD), and the absolute configurations of compounds 1 and 4 were determined by single-crystal X-ray crystallography. Compounds 1 and 2 represent the first unusual cyathane acetals featuring a dioxolane ring. Compounds 1-6 displayed differential nerve growth factor-induced neurite outgrowth-promoting activity in PC-12 cells at concentrations of 10 μM. In addition, cyahookerin B (2), cyathin E (9), cyathin B2 (12), and cyathin Q (13) showed significant nitric oxide production inhibition in Lipopolysaccharide (LPS)-activated BV-2 microglial cells with IC50 values of 12.0, 6.9, 10.9, and 9.1 μM, respectively. Similar binding modes of the four compounds were indicated by molecular-docking studies, and structure-activity relationships are discussed.
  • Two cytotoxic triterpenes from cultures of a Kenyan Laetiporus sp. (Basidiomycota)

    Chepkirui, Clara; Matasyoh, Josphat, C.; Decock, Cony, A.; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2017-04-26)
    HPLC profiling of the mycelial culture of a poroid basidomycete collected in Mount Elgon, Kenya, which probably represents a new species of the genus Laetiporus, led to isolation of two previously undescribed lanostane type triterpenes.We propose the trivial names laetiporins A (1) and B (2). In addition, five known ones: dehydrosulphurenic acid (3), sulphurenic acid (4), eburicoic acid (5), 15α-hydroxytrametenolic acid (6) and trametenolic acid (7) were also isolated. The laetiporins (1–2) exhibited significant cytotoxic effects against various human cancer cells. The known compounds (3–5) and (7) also showed moderate cytotoxic activity, but none of the compounds showed any significant antimicrobial activity.
  • Fungal diversity notes 929–1035: taxonomic and phylogenetic contributions on genera and species of fungi

    Phookamsak, Rungtiwa; Stadler, Mark; et al.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Springer-Nature, 2019-05-01)
    This article is the ninth in the series of Fungal Diversity Notes, where 107 taxa distributed in three phyla, nine classes, 31 orders and 57 families are described and illustrated. Taxa described in the present study include 12 new genera, 74 new species, three new combinations, two reference specimens, a re-circumscription of the epitype, and 15 records of sexual-asexual morph connections, new hosts and new geographical distributions. Twelve new genera comprise Brunneofusispora, Brunneomurispora, Liua, Lonicericola, Neoeutypella, Paratrimmatostroma, Parazalerion, Proliferophorum, Pseudoastrosphaeriellopsis, Septomelanconiella, Velebitea and Vicosamyces. Seventy-four new species are Agaricus memnonius, A. langensis, Aleurodiscus patagonicus, Amanita flavoalba, A. subtropicana, Amphisphaeria mangrovei, Baorangia major, Bartalinia kunmingensis, Brunneofusispora sinensis, Brunneomurispora lonicerae, Capronia camelliae-yunnanensis, Clavulina thindii, Coniochaeta simbalensis, Conlarium thailandense, Coprinus trigonosporus, Liua muriformis, Cyphellophora filicis, Cytospora ulmicola, Dacrymyces invisibilis, Dictyocheirospora metroxylonis, Distoseptispora thysanolaenae, Emericellopsis koreana, Galiicola baoshanensis, Hygrocybe lucida, Hypoxylon teeravasati, Hyweljonesia indica, Keissleriella caraganae, Lactarius olivaceopallidus, Lactifluus midnapurensis, Lembosia brigadeirensis, Leptosphaeria urticae, Lonicericola hyaloseptispora, Lophiotrema mucilaginosis, Marasmiellus bicoloripes, Marasmius indojasminodorus, Micropeltis phetchaburiensis, Mucor orantomantidis, Murilentithecium lonicerae, Neobambusicola brunnea, Neoeutypella baoshanensis, Neoroussoella heveae, Neosetophoma lonicerae, Ophiobolus malleolus, Parabambusicola thysanolaenae, Paratrimmatostroma kunmingensis, Parazalerion indica, Penicillium dokdoense, Peroneutypa mangrovei, Phaeosphaeria cycadis, Phanerochaete australosanguinea, Plectosphaerella kunmingensis, Plenodomus artemisiae, P. lijiangensis, Proliferophorum thailandicum, Pseudoastrosphaeriellopsis kaveriana, Pseudohelicomyces menglunicus, Pseudoplagiostoma mangiferae, Robillarda mangiferae, Roussoella elaeicola, Russula choptae, R. uttarakhandia, Septomelanconiella thailandica, Spencermartinsia acericola, Sphaerellopsis isthmospora, Thozetella lithocarpi, Trechispora echinospora, Tremellochaete atlantica, Trichoderma koreanum, T. pinicola, T. rugulosum, Velebitea chrysotexta, Vicosamyces venturisporus, Wojnowiciella kunmingensis and Zopfiella indica. Three new combinations are Baorangia rufomaculata, Lanmaoa pallidorosea and Wojnowiciella rosicola. The reference specimens of Canalisporium kenyense and Tamsiniella labiosa are designated. The epitype of Sarcopeziza sicula is re-circumscribed based on cyto- and histochemical analyses. The sexual-asexual morph connection of Plenodomus sinensis is reported from ferns and Cirsium for the first time. In addition, the new host records and country records are Amanita altipes, A. melleialba, Amarenomyces dactylidis, Chaetosphaeria panamensis, Coniella vitis, Coprinopsis kubickae, Dothiorella sarmentorum, Leptobacillium leptobactrum var. calidus, Muyocopron lithocarpi, Neoroussoella solani, Periconia cortaderiae, Phragmocamarosporium hederae, Sphaerellopsis paraphysata and Sphaeropsis eucalypticola.
  • New terpenoids from the fermentation broth of the edible mushroom .

    Surup, Frank; Hennicke, Florian; Sella, Nadine; Stroot, Maria; Bernecker, Steffen; Pfütze, Sebastian; Stadler, Marc; Rühl, Martin; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Beilstein Institut, 2019-01-01)
    The strophariaceous basidiomycete Cyclocybe aegerita (synonyms Agrocybe aegerita and A. cylindracea) is one of the most praised cultivated edible mushrooms and is being cultivated at large scale for food production. Furthermore, the fungus serves as a model organism to study fruiting body formation and the production of secondary metabolites during the life cycle of Basidiomycota. By studying the secondary metabolite profiles of C. aegerita, we found several terpenoids in submerged cultures. Aside from the main metabolite, bovistol (1), two new bovistol derivatives B and C (2, 3) and pasteurestin C as a new protoilludane (4) were isolated by preparative HPLC. Their structures were elucidated by mass spectrometry and NMR spectroscopy. The relative configurations of 2-4 were assigned by ROESY correlations, and 3JH,H coupling constants in the case of 4. Applying quantitative PCR for gene expression validation, we linked the production of bovistol and its derivatives to the respective biosynthesis gene clusters.
  • Sesquiterpenes from an Eastern African Medicinal Mushroom Belonging to the Genus Sanghuangporus.

    Cheng, Tian; Chepkirui, Clara; Decock, Cony; Matasyoh, Josphat Clement; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (American Cemical Society (ACS), 2019-05-24)
    During the course of searching for new anti-infective and other biologically active secondary metabolites from Kenyan basidiomycetes, 13 previously undescribed metabolites, (6 R,7 S,10 R)-7,10-epoxy-7,11-dimethyldodec-1-ene-6,11-diol (1) and 12 sesquiterpenes named elgonenes A-L (2-13), and the known compound P-coumaric acid (14) were isolated from a basidiomycete collected in Mount Elgon Natural Reserve. The producing organism represents a new species of the genus Sanghuangporus, which is one of the segregates of the important traditional Asian medicinal mushrooms that were formerly known as the " Inonotus linteus" complex. The structure elucidation of compounds 1-13, based on 2D NMR spectroscopy, high-resolution mass spectrometry, and other spectral methods, and their antibacterial, antifungal, and cytotoxic activities are reported.
  • 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.
  • Cytotoxic, antimicrobial and antiviral secondary metabolites produced by the plant pathogenic fungus Cytospora sp. CCTU A309.

    Narmani, Abolfazl; Teponno, Rémy Bertrand; Arzanlou, Mahdi; Surup, Frank; Helaly, Soleiman E; Wittstein, Kathrin; Praditya, Dimas F; Babai-Ahari, Asadollah; Steinmann, Eike; Stadler, Marc; et al. (Elsevier, 2019-04-01)
    Chemical analysis of extracts from cultures of the plant pathogenic fungus Cytospora sp. strain CCTU A309 collected in Iran led to the isolation of two previously unreported heptanedioic acid derivatives namely (2R,3S) 2-hydroxy-3-phenyl-4-oxoheptanedioic acid (1) and (2S,3S) 2-hydroxy-3-phenyl-4-oxoheptanedioic acid (2) as diastereomers, four previously undescribed prenylated p-terphenyl quinones 3-6 in addition to five known metabolites. Their structures were elucidated on the basis of extensive spectroscopic analysis and high-resolution mass spectrometry. For metabolites 1 and 2, the absolute configurations at C-2 were deduced from comparison of the 1H NMR difference of their (S)- and (R)-phenylglycine methyl ester derivatives while the relative configurations were tentatively assigned by a J-based analysis and confirmed by comparison of 13C chemical shifts to literature data. The isolated compounds were tested for their cytotoxic, antimicrobial (including biofilm inhibition), antiviral, and nematicidal activities. While only moderate antimicrobial effects were observed, the terphenyl quinone derivatives 3-6 and leucomelone (10) exhibited significant cytotoxicity against the mouse fibroblast L929 and cervix carcinoma KB-3-1 cell lines with IC50 values ranging from 2.4 to 26 μg/mL. Furthermore, metabolites 4-6 showed interesting antiviral activity against hepatitis C virus (HCV).
  • Antiviral Meroterpenoid Rhodatin and Sesquiterpenoids Rhodocoranes A-E from the Wrinkled Peach Mushroom, Rhodotus palmatus.

    Sandargo, Birthe; Michehl, Maira; 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. (American Chemical Society, 2019-05-03)
    Rhodatin (1), a meroterpenoid featuring a unique pentacyclic scaffold with both spiro and spiroketal centers, and five unusual acorane-type sesquiterpenoids, named rhodocoranes A-E (2-6, respectively), are the first natural products isolated from the basidiomycete Rhodotus palmatus. Their structures were elucidated by two-dimensional NMR experiments and HRESIMS, while the absolute configuration of the substance family was determined by Mosher's method utilizing 2. Rhodatin strongly inhibited hepatitis C virus, whereas 4 displayed cytotoxicity and selective antifungal activity.
  • Cystobactamids 920-1 and 920-2: Assignment of the Constitution and Relative Configuration by Total Synthesis.

    Planke, Therese; Moreno, María; Hüttel, Stephan; Fohrer, Jörg; Gille, Franziska; Norris, Matthew D; Siebke, Maik; Wang, Liangliang; Müller, Rolf; Kirschning, Andreas; et al. (ACS Publications, 2019-03-01)
    Total synthesis of cystobactamid 920-1 and its epimer has allowed an unambiguous assignment of the relative and absolute configuration of the natural product. A careful structural analysis of each isomer using both NMR and computational techniques also prompted a constitutional revision of the structures originally reported for cystobactamids 920-1 and 920-2, and has provided further insight into the unique conformational preferences of the cystobactamid family
  • 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.

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