• 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; et al. (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.
    • 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.
    • Akanthopyrones A-D, α-Pyrones Bearing a 4-O-Methyl-β-d-glucopyranose Moiety from the Spider-Associated Ascomycete Akanthomyces novoguineensis.

      Kuephadungphan, Wilawan; Helaly, Soleiman E; Daengrot, Charuwan; Phongpaichit, Souwalak; Luangsa-Ard, Janet Jennifer; Rukachaisirikul, Vatcharin; Stadler, Marc; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-07-18)
      Hypocrealean fungi have proved to be prolific bioactive metabolite producers; they have caught the attention of mycologists throughout the world. However, only a few studies on the insect and spider parasitic genus Akanthomyces have so far been carried out. In this study, we report the isolation, structural elucidation and biological activities of four unprecedented glycosylated α-pyrone derivatives, akanthopyrones A-D (1-4), from a culture of Akanthomyces novoguineensis collected in Thailand. The chemical structures of the akanthopyrones were determined by extensive 1D- and 2D-NMR, and HRMS spectroscopic analysis. Their absolute configurations were determined. Akanthopyrone A (1) exhibited weak antimicrobial activity against Bacillus subtilis DSM10 and cytotoxicity against the HeLa cell line KB-3-1, while akanthopyrone D (4) showed weak activity against Candida tenuis MUCL 29892.
    • 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.
    • 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.
    • 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.
    • 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.
    • The application of the name Xylaria hypoxylon, based on Clavaria hypoxylon of Linnaeus.

      Stadler, Marc; Hawksworth, David L; Fournier, Jacques (2014-06)
      Although Xylaria hypoxylon is one of the most familiar fungi of temperate regions, the basionym of the name, Clavaria hypoxylon of Linnaeus, has remained untypified. Here we assess the original five elements included in the 1753 protologue; no candidate specimen was located but two illustrations Linnaeus cited were considered, one a mixture of species and the other fanciful. As the name is sanctioned, following clarifications in the Melbourne Code, elements cited by Fries when the name was sanctioned in 1823 are also candidates for lectotypification. In addition to various illustrations, Fries cites two exsiccatae, and one from his own Scleromycetes Suecicae distributed in 1821 is designated as lectotype for Linnaeus' name here. In view of the complexity of the group as revealed by molecular systematic work, and the poor state of the Fries material, we also designate a sequenced epitype from Sweden. We stress the importance of examining fungi in the complex in the sexual state, as those that are asexual can be difficult to identify conclusively. Figures of the original protologues and the most pertinent illustrations and specimens are provided, along with a detailed description and illustrations based on recent collections.
    • 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)
    • Bacterial type III polyketide synthases: phylogenetic analysis and potential for the production of novel secondary metabolites by heterologous expression in pseudomonads.

      Gross, Frank; Luniak, Nora; Perlova, Olena; Gaitatzis, Nikolaos; Jenke-Kodama, Holger; Gerth, Klaus; Gottschalk, Daniela; Dittmann, Elke; Müller, Rolf (2006-03-01)
      Type III polyketide synthases (PKS) were regarded as typical for plant secondary metabolism before they were found in microorganisms recently. Due to microbial genome sequencing efforts, more and more type III PKS are found, most of which of unknown function. In this manuscript, we report a comprehensive analysis of the phylogeny of bacterial type III PKS and report the expression of a type III PKS from the myxobacterium Sorangium cellulosum in pseudomonads. There is no precedent of a secondary metabolite that might be biosynthetically correlated to a type III PKS from any myxobacterium. Additionally, an inactivation mutant of the S. cellulosum gene shows no physiological difference compared to the wild-type strain which is why these type III PKS are assumed to be "silent" under the laboratory conditions administered. One type III PKS (SoceCHS1) was expressed in different Pseudomonas sp. after the heterologous expression in Escherichia coli failed. Cultures of recombinant Pseudomonas sp. harbouring SoceCHS1 turned red upon incubation and the diffusible pigment formed was identified as 2,5,7-trihydroxy-1,4-naphthoquinone, the autooxidation product of 1,3,6,8-tetrahydroxynaphthalene. The successful heterologous production of a secondary metabolite using a gene not expressed under administered laboratory conditions provides evidence for the usefulness of our approach to activate such secondary metabolite genes for the production of novel metabolites.
    • Bioactive Compounds Produced by Hypoxylon fragiforme against Staphylococcus aureus Biofilms.

      Yuyama, Kamila Tomoko; Chepkirui, Clara; Wendt, Lucile; Fortkamp, Diana; Stadler, Marc; Abraham, Wolf-Rainer; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-12-12)
      Treating infections organized in biofilms is a challenge due to the resistance of the pathogens against antibiotics and host immune cells. Many fungi grow in a wet environment, favorable for the growth of bacterial biofilms, and we speculated that fungi possess some strategies to control these bacterial biofilms. A fungus identified as Hypoxylon fragiforme, was collected in the Harz Mountains, Germany, and its mycelial culture was fermented in different culture media for 67 days to test its biological potential against bacterial biofilms. Sclerin, sclerin diacid and its 3-methyl monoester (methyl 1-(5-hydroxy-6-carboxylic-2,3,4-trimethylphenyl) propionate) are here described for the first time from this fungus. Sclerin and its diacid interfered with the biofilm formation of the pathogen Staphylococcus aureus, inhibiting 86% and 80% of the biofilm at 256 μg mL-1, respectively, but not killing the bacterium. Interestingly, the monomethylester of sclerin diacid was inactive. Although these compounds did not possess any activity against a pre-formed biofilm, they prevented its formation at subtoxic concentrations. Furthermore, sclerin and its diacid displayed a high specificity against Staphylococcus aureus, indicating a good strategy against pathogenic biofilms when combined with antibiotics.
    • 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.
    • Botryane, noreudesmane and abietane terpenoids from the ascomycete Hypoxylon rickii.

      Kuhnert, Eric; Surup, Frank; Wiebach, Vincent; Bernecker, Steffen; Stadler, Marc; Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany. (2015-09)
      In the course of our screening for new bioactive natural products, a culture of Hypoxylon rickii, a xylariaceous ascomycete collected from the Caribbean island Martinique, was identified as extraordinary prolific producer of secondary metabolites. Ten metabolites of terpenoid origin were isolated from submerged cultures of this species by preparative HPLC. Their structures were elucidated using spectral techniques including 2D NMR and HRESIMS. Three of the compounds were elucidated as new botryanes (1-3) along with three known ones, i.e. (3aS)-3a,5,5,8-tetramethyl-3,3a,4,5-tetrahydro-1H-cyclopenta[de]isochromen-1-one (4), (3aS,8R)-3a,5,5,8-tetramethyl-3,3a,4,5,7,8-hexahydro-1H-cyclopenta[de]isochromen-1-one (5) and botryenanol (6). Further three new sesquiterpenoids featured a 14-noreudesmane-type skeleton and were named hypoxylan A-C (7-9); the diterpenoid rickitin A (10) contains an abietane-type backbone. Compounds 1, 2, 3, 7, and 10 showed cytotoxic effects against murine cells.
    • Carolacton - A macrolide ketocarbonic acid that reduces biofilm formation by the caries- and endocarditis-associated bacterium Streptococcus mutans

      Jansen, Rolf; Microbial Drugs, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig (Germany) (Wiley Interscience, 2010-03)
    • Characterizing the Epothilone Binding Site on β-Tubulin by Photoaffinity Labeling: Identification of β-Tubulin Peptides TARGSQQY and TSRGSQQY as Targets of an Epothilone Photoprobe for Polymerized Tubulin.

      Ranade, Adwait R; Higgins, LeeAnn; Markowski, Todd W; Glaser, Nicole; Kashin, Dmitry; Bai, Ruoli; Hong, Kwon Ho; Hamel, Ernest; Höfle, Gerhard; Georg, Gunda I; et al. (2016-04-14)
      Photoaffinity labeling with an epothilone A photoprobe led to the identification of the β-tubulin peptides TARGSQQY and TSRGSQQY as targets of the photoprobe for polymerized tubulin. These peptides represent residues 274-281 in different β-tubulin isotypes. Placing the carbene producing 21-diazo/triazolo moiety of the photoprobe in the vicinity of the TARGSQQY peptide in a homology model of TBB3 predicted a binding pose and conformation of the photoprobe that are very similar to the ones reported for 1) the high resolution cocrystal structure of epothilone A with an α,β-tubulin complex and for 2) a saturation transfer difference NMR and transferred NOESY NMR study of dimeric and polymerized tubulin. Our findings thus provide additional support for these models as physiologically the most relevant among several modes of binding that have been proposed for epothilone A in the taxane pocket of β-tubulin.
    • Chlorotonil A, a macrolide with a unique gem-dichloro-1,3-dione functionality from Sorangium cellulosum, So ce1525.

      Gerth, Klaus; Steinmetz, Heinrich; Höfle, Gerhard; Jansen, Rolf; Helmholtz-Zentrum für Infektionsforschung, Inhoffenstrasse 7, 38124 Braunschweig, Germany. (2008)
    • 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; et al. (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.
    • 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.
    • Cyclic depsipeptides, ichthyopeptins A and B, from Microcystis ichthyoblabe.

      Zainuddin, Elmi N; Mentel, Renate; Wray, Victor; Jansen, Rolf; Nimtz, Manfred; Lalk, Michael; Mundt, Sabine; Institute of Pharmacy, Friedrich-Ludwig-Jahnstrasse 17, Ernst-Moritz-Arndt University, D-17487 Greifswald, Germany. (2007-07)
      Bioassay-guided isolation of antiviral compounds from the cultured cyanobacterium Microcystis ichthyoblabe provided two novel cyclic depsipeptides, ichthyopeptins A (1) and B (2). Their structures were determined by 1D (1H and 13C) and 2D (COSY, TOCSY, ROESY, HMQC, and HMBC) NMR spectra, ESIMS-MS, and amino acid analysis. The fraction containing both cyclic depsipeptides exhibited antiviral activity against influenza A virus with an IC50 value of 12.5 microg/mL.