William H Gerwick

Publications (161)730.16 Total impact

• Article: Mycoleptodiscins A and B, Cytotoxic Alkaloids from the Endophytic Fungus Mycoleptodiscus sp. F0194.

  Humberto E Ortega, Paul R Graupner, Yumi Asai, Karen Tendyke, Dayong Qiu, Young Yongchun Shen, Nivia Rios, A Elizabeth Arnold, Phyllis D Coley, Thomas A Kursar, William H Gerwick, Luis Cubilla-Rios
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  ABSTRACT: Two novel reddish-orange alkaloids, mycoleptodiscin A (1) and mycoleptodiscin B (2), were isolated from liquid cultures of the endophytic fungus Mycoleptodiscus sp. that had been isolated from Desmotes incomparabilis in Panama. Elucidation of their structures was accomplished using 1D and 2D NMR spectroscopy in combination with IR spectroscopic and MS data. These compounds are indole-terpenes with a new skeleton uncommon in nature. Mycoleptodiscin B (2) was active in inhibiting the growth of cancer cell lines with IC50 values in the range 0.60-0.78 μM.
  Journal of Natural Products 04/2013; · 3.13 Impact Factor
• Article: Phylogenetic Inferences Reveal Large Extent of Novel Biodiversity in Chemically Rich Tropical Marine Cyanobacteria.

  Niclas Engene, Sarath P Gunasekera, William H Gerwick, Valerie J Paul
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  ABSTRACT: Benthic marine cyanobacteria are known for their prolific biosynthetic capacities to produce structurally diverse secondary metabolites with biomedical application and their ability to form cyanobacterial harmful algal blooms. In an effort to provide taxonomic clarity to better guide future natural products drug discovery investigations and harmful algal bloom monitoring, this study investigated the taxonomy of tropical and subtropical natural product-producing marine cyanobacteria based on their evolutionary relatedness. Our phylogenetic inferences of marine cyanobacterial strains responsible for over 100 bioactive secondary metabolites reveal an uneven taxonomic distribution with a few groups being responsible for the vast majority of these molecules. Our data also suggest a high degree of novel biodiversity among natural product-producing strains that previously was overlooked by traditional morphology-based taxonomic approaches. This unrecognized biodiversity is primarily due to a lack of proper classification systems since the taxonomy of tropical and subtropical, benthic marine cyanobacteria has only recently been analyzed by phylogenetic methods. This evolutionary study provides a framework for a more robust classification system to better understand the taxonomy of tropical and subtropical marine cyanobacteria and the distribution of natural products in marine cyanobacteria.
  Applied and environmental microbiology 01/2013; · 3.69 Impact Factor
• Source

  Available from: Vítor Ramos

  Article: Chemoecological screening reveals high bioactivity in diverse culturable portuguese marine cyanobacteria.

  Pedro N Leão, Vitor Ramos, Patrício B Gonçalves, Flávia Viana, Olga M Lage, William H Gerwick, Vitor M Vasconcelos
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  ABSTRACT: Marine cyanobacteria, notably those from tropical regions, are a rich source of bioactive secondary metabolites. Tropical marine cyanobacteria often grow to high densities in the environment, allowing direct isolation of many secondary metabolites from field-collected material. However, in temperate environments culturing is usually required to produce enough biomass for investigations of their chemical constituents. In this work, we cultured a selection of novel and diverse cyanobacteria isolated from the Portuguese coast, and tested their organic extracts in a series of ecologically-relevant bioassays. The majority of the extracts showed activity in at least one of the bioassays, all of which were run in very small scale. Phylogenetically related isolates exhibited different activity profiles, highlighting the value of microdiversity for bioprospection studies. Furthermore, LC-MS analyses of selected active extracts suggested the presence of previously unidentified secondary metabolites. Overall, the screening strategy employed here, in which previously untapped cyanobacterial diversity was combined with multiple bioassays, proved to be a successful strategy and allowed the selection of several strains for further investigations based on their bioactivity profiles.
  Marine Drugs 01/2013; 11(4):1316-35. · 3.85 Impact Factor
• Article: Drug Discovery from Marine Microbes.

  William H Gerwick, Amanda M Fenner
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  ABSTRACT: The marine environment has been a source of more than 20,000 inspirational natural products discovered over the past 50 years. From these efforts, 9 approved drugs and 12 current clinical trial agents have been discovered, either as natural products or as molecules inspired from the natural product structure. To a significant degree, these have come from collections of marine invertebrates largely obtained from shallow-water tropical ecosystems. However, there is a growing recognition that marine invertebrates are oftentimes populated with enormous quantities of "associated" or symbiotic microorganisms and that microorganisms are the true metabolic sources of these most valuable of marine natural products. Also, because of the inherently multidisciplinary nature of this field, a high degree of innovation is characteristic of marine natural product drug discovery efforts.
  Microbial Ecology 12/2012; · 2.91 Impact Factor
• Article: Heterologous Production of 4-O-Demethylbarbamide, a Marine Cyanobacterial Natural Product.

  Eun Ji Kim, Jong Hyun Lee, Hyukjae Choi, Alban R Pereira, Yeon Hee Ban, Young Ji Yoo, Eunji Kim, Je Won Park, David H Sherman, William H Gerwick, Yeo Joon Yoon
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  ABSTRACT: Heterologous expression of the barbamide biosynthetic gene cluster, obtained from the marine cyanobacterium Moorea producens, in the terrestrial actinobacterium Streptomyces venezuelae, resulted in the production of a new barbamide congener 4-O-demethylbarbamide, demonstrating the potential of this approach for investigating the assembly and tailoring of complex marine natural products.
  Organic Letters 11/2012; · 5.86 Impact Factor
• Source

  Available from: Thomas Murray

  Article: Bidirectional influence of sodium channel activation on NMDA receptor-dependent cerebrocortical neuron structural plasticity.

  Joju George, Daniel G Baden, William H Gerwick, Thomas F Murray
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  ABSTRACT: Neuronal activity regulates brain development and synaptic plasticity through N-methyl-d-aspartate receptors (NMDARs) and calcium-dependent signaling pathways. Intracellular sodium ([Na(+)](i)) also exerts a regulatory influence on NMDAR channel activity, and [Na(+)](i) may, therefore, function as a signaling molecule. In an attempt to mimic the influence of neuronal activity on synaptic plasticity, we used brevetoxin-2 (PbTx-2), a voltage-gated sodium channel (VGSC) gating modifier, to manipulate [Na(+)](i) in cerebrocortical neurons. The acute application of PbTx-2 produced concentration-dependent increments in both intracellular [Na(+)] and [Ca(2+)]. Pharmacological evaluation showed that PbTx-2-induced Ca(2+) influx primarily involved VGSC activation and NMDAR-mediated entry. Additionally, PbTx-2 robustly potentiated NMDA-induced Ca(2+) influx. PbTx-2-exposed neurons showed enhanced neurite outgrowth, increased dendritic arbor complexity, and increased dendritic filopodia density. The appearance of spontaneous calcium oscillations, reflecting synchronous neuronal activity, was accelerated by PbTx-2 treatment. Parallel to this response, PbTx-2 increased cerebrocortical neuron synaptic density. PbTx-2 stimulation of neurite outgrowth, dendritic arborization, and synaptogenesis all exhibited bidirectional concentration-response profiles. This profile paralleled that of NMDA, which also produced bidirectional concentration-response profiles for neurite outgrowth and synaptogenesis. These data are consistent with the hypothesis that PbTx-2-enhanced neuronal plasticity involves NMDAR-dependent signaling. Our results demonstrate that PbTx-2 mimics activity-dependent neuronal structural plasticity in cerebrocortical neurons through an increase in [Na(+)](i), up-regulation of NMDAR function, and engagement of downstream Ca(2+)-dependent signaling pathways. These data suggest that VGSC gating modifiers may represent a pharmacologic strategy to regulate neuronal plasticity through NMDAR-dependent mechanisms.
  Proceedings of the National Academy of Sciences 11/2012; · 9.68 Impact Factor
• Source

  Available from: Lena Gerwick

  Article: Structural Basis of Functional Group Activation by Sulfotransferases in Complex Metabolic Pathways.

  Jennifer Gehret McCarthy, Eli B Eisman, Sarang Kulkarni, Lena Gerwick, William H Gerwick, Peter Wipf, David H Sherman, Janet L Smith
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  ABSTRACT: Sulfated molecules with diverse functions are common in biology, but sulfonation as a method to activate a metabolite for chemical catalysis is rare. Catalytic activity was characterized and crystal structures were determined for two such "activating" sulfotransferases (STs) that sulfonate β-hydroxyacyl thioester substrates. The CurM polyketide synthase (PKS) ST domain from the curacin A biosynthetic pathway of Moorea producens and the olefin synthase (OLS) ST from a hydrocarbon-producing system of Synechococcus PCC 7002 both occur as a unique acyl carrier protein (ACP), ST, and thioesterase (TE) tridomain within a larger polypeptide. During pathway termination, these cyanobacterial systems introduce a terminal double bond into the β-hydroxyacyl-ACP-linked substrate by the combined action of the ST and TE. Under in vitro conditions, CurM PKS ST and OLS ST acted on β-hydroxy fatty acyl-ACP substrates; however, OLS ST was not reactive toward analogues of the natural PKS ST substrate bearing a C5-methoxy substituent. The crystal structures of CurM ST and OLS ST revealed that they are members of a distinct protein family relative to other prokaryotic and eukaryotic sulfotransferases. A common binding site for the sulfonate donor 3'-phosphoadenosine-5'-phosphosulfate was visualized in complexes with the product 3'-phosphoadenosine-5'-phosphate. Critical functions for several conserved amino acids in the active site were confirmed by site-directed mutagenesis, including a proposed glutamate catalytic base. A dynamic active-site flap unique to the "activating" ST family affects substrate selectivity and product formation, based on the activities of chimeras of the PKS and OLS STs with exchanged active-site flaps.
  ACS Chemical Biology 09/2012; · 6.45 Impact Factor
• Article: Viequeamide a, a cytotoxic member of the kulolide superfamily of cyclic depsipeptides from a marine button cyanobacterium.

  Paul D Boudreau, Tara Byrum, Wei-Ting Liu, Pieter C Dorrestein, William H Gerwick
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  ABSTRACT: The viequeamides, a family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, were isolated from a shallow subtidal collection of a "button" cyanobacterium (Rivularia sp.) from near the island of Vieques, Puerto Rico. Planar structures of the two major compounds, viequeamide A (1) and viequeamide B (2), were elucidated by 2D-NMR spectroscopy and mass spectrometry, whereas absolute configurations were determined by traditional hydrolysis, derivative formation, and chromatography in comparison with standards. In addition, a series of related minor metabolites, viequeamides C-F (3-6), were characterized by HRMS fragmentation methods. Viequeamide A was found to be highly toxic to H460 human lung cancer cells (IC(50) = 60 ± 10 nM), whereas the mixture of B-F was inactive. From a broader perspective, the viequeamides help to define a "superfamily" of related cyanobacterial natural products, the first of which to be discovered was kulolide. Within the kulolide superfamily, a wide variation in biological properties is observed, and the reported producing strains are also highly divergent, giving rise to several intriguing questions about structure-activity relationships and the evolutionary origins of this metabolite class.
  Journal of Natural Products 08/2012; 75(9):1560-70. · 3.13 Impact Factor
• Article: Coibacins A-D, antileishmanial marine cyanobacterial polyketides with intriguing biosynthetic origins.

  Marcy J Balunas, Manuel F Grosso, Francisco A Villa, Niclas Engene, Kerry L McPhail, Kevin Tidgewell, Laura M Pineda, Lena Gerwick, Carmenza Spadafora, Dennis E Kyle, William H Gerwick
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  ABSTRACT: Four unsaturated polyketide lactone derivatives, coibacins A-D, were isolated from a Panamanian marine cyanobacterium, cf. Oscillatoria sp. The two different types of termini observed in these co-occurring metabolites, either a methyl cyclopropyl ring as seen in curacin A or a methyl vinyl chloride similar to that observed in the jamaicamides, suggest an intriguing flexibility in the "beta branch" forming biosynthetic process. The coibacins possess selective antileishmanial activity as well as potent anti-inflammatory activity.
  Organic Letters 07/2012; 14(15):3878-81. · 5.86 Impact Factor
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  Available from: Jan Kaštovský

  Article: Moorea producens gen. nov., sp. nov. and Moorea bouillonii comb. nov., tropical marine cyanobacteria rich in bioactive secondary metabolites.

  Niclas Engene, Erin C Rottacker, Jan Kaštovský, Tara Byrum, Hyukjae Choi, Mark H Ellisman, Jiří Komárek, William H Gerwick
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  ABSTRACT: The filamentous cyanobacterial genus Moorea gen. nov., described here under the provisions of the International Code of Botanical Nomenclature, is a cosmopolitan pan-tropical group abundant in the marine benthos. Members of the genus Moorea are photosynthetic (containing phycocyanin, phycoerythrin, allophycocyanin and chlorophyll a), but non-diazotrophic (lack heterocysts and nitrogenase reductase genes). The cells (discoid and 25-80 µm wide) are arranged in long filaments (<10 cm in length) and often form extensive mats or blooms in shallow water. The cells are surrounded by thick polysaccharide sheaths covered by a rich diversity of heterotrophic micro-organisms. A distinctive character of this genus is its extraordinarily rich production of bioactive secondary metabolites. This is matched by genomes rich in polyketide synthase and non-ribosomal peptide synthetase biosynthetic genes which are dedicated to secondary metabolism. The encoded natural products are sometimes responsible for harmful algae blooms and, due to morphological resemblance to the genus Lyngbya, this group has often been incorrectly cited in the literature. We here describe two species of the genus Moorea: Moorea producens sp. nov. (type species of the genus) with 3L(T) as the nomenclature type, and Moorea bouillonii comb. nov. with PNG5-198(R) as the nomenclature type.
  INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY 07/2012; 62(Pt 5):1171-8. · 2.11 Impact Factor
• Article: Observing the invisible through imaging mass spectrometry, a window into the metabolic exchange patterns of microbes.

  David J Gonzalez, Yuquan Xu, Yu-Liang Yang, Eduardo Esquenazi, Wei-Ting Liu, Anna Edlund, Tram Duong, Liangcheng Du, István Molnár, William H Gerwick, Paul R Jensen, Michael Fischbach, Chih-Chuang Liaw, Paul Straight, Victor Nizet, Pieter C Dorrestein
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  ABSTRACT: Many microbes can be cultured as single-species communities. Often, these colonies are controlled and maintained via the secretion of metabolites. Such metabolites have been an invaluable resource for the discovery of therapeutics (e.g. penicillin, taxol, rapamycin, epothilone). In this article, written for a special issue on imaging mass spectrometry, we show that MALDI-imaging mass spectrometry can be adapted to observe, in a spatial manner, the metabolic exchange patterns of a diverse array of microbes, including thermophilic and mesophilic fungi, cyanobacteria, marine and terrestrial actinobacteria, and pathogenic bacteria. Dependent on media conditions, on average and based on manual analysis, we observed 11.3 molecules associated with each microbial IMS experiment, which was split nearly 50:50 between secreted and colony-associated molecules. The spatial distributions of these metabolic exchange factors are related to the biological and ecological functions of the organisms. This work establishes that MALDI-based IMS can be used as a general tool to study a diverse array of microbes. Furthermore the article forwards the notion of the IMS platform as a window to discover previously unreported molecules by monitoring the metabolic exchange patterns of organisms when grown on agar substrates.
  Journal of proteomics 05/2012; 75(16):5069-76. · 5.07 Impact Factor
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  Available from: Lena Gerwick

  Article: Honaucins A-C, potent inhibitors of inflammation and bacterial quorum sensing: synthetic derivatives and structure-activity relationships.

  Hyukjae Choi, Samantha J Mascuch, Francisco A Villa, Tara Byrum, Margaret E Teasdale, Jennifer E Smith, Linda B Preskitt, David C Rowley, Lena Gerwick, William H Gerwick
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  ABSTRACT: Honaucins A-C were isolated from the cyanobacterium Leptolyngbya crossbyana which was found overgrowing corals on the Hawaiian coast. Honaucin A consists of (S)-3-hydroxy-γ-butyrolactone and 4-chlorocrotonic acid, which are connected via an ester linkage. Honaucin A and its two natural analogs exhibit potent inhibition of both bioluminescence, a quorum-sensing-dependent phenotype, in Vibrio harveyi BB120 and lipopolysaccharide-stimulated nitric oxide production in the murine macrophage cell line RAW264.7. The decrease in nitric oxide production was accompanied by a decrease in the transcripts of several proinflammatory cytokines, most dramatically interleukin-1β. Synthesis of honaucin A, as well as a number of analogs, and subsequent evaluation in anti-inflammation and quorum-sensing inhibition bioassays revealed the essential structural features for activity in this chemical class and provided analogs with greater potency in both assays.
  Chemistry & biology 05/2012; 19(5):589-98. · 6.52 Impact Factor
• Article: Linking bioprospecting with sustainable development and conservation: the Panama case

  Thomas A. Kursar, Catherina C. Caballero-George, Todd L. Capson, Luis Cubilla-Rios, William H. Gerwick, Maria V. Heller, Alicia Ibañez, Roger G. Linington, Kerry L. McPhail, Eduardo Ortega-Barría, Luz I. Romero, P. D. Coley
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  ABSTRACT: The limited international resources for economic aid and conservation can only mitigate poverty and losses of biodiversity. Hence, developing nations must establish the capacity to resolve their problems. Additionally, policy-makers and donors need to obtain scientific input on issues such as global change and ecosystem services. We propose that for nations rich in biodiversity, ecosystem services derived from bioprospecting, or drug discovery, could contribute to economic development. In the case where unstudied samples are shipped abroad for research, the chances of obtaining royalties are infinitesimally small. Therefore developing nations will only realize benefits from bioprospecting through in-country research on their own biodiversity. Policy-makers and donors have failed to appreciate the value of this approach. In order to provide an example of the inherent links between conservation and sustainable economic development, we initiated a drug discovery effort in Panama that emphasizes local benefit. As much of the drug discovery process as possible is conducted in Panamanian laboratories, providing jobs dependent on intact biodiversity and enhancing local research and training. In short, research, plus the spin-offs from research, provide immediate and long-lasting benefits to Panama. The connection between conservation and development has been highlighted in publicity about the project in Panama’s urban media. This provides a constructive alternative to the perception the among the urban populace that economic development inevitably competes with conservation. In summary, our program uses biodiversity to promote human health as well as to support research capacity, economic development and conservation within Panama. The program provides an example of the widely recognized but little developed concept of bioprospecting research as an ecosystem service. KeywordsBioprospecting-Chagas’ disease-Convention on biological diversity-Ecosystem services-ICBG-Leishmaniasis-Malaria-Panama-Policy-makers-Sustainable development
  Biodiversity and Conservation 04/2012; 16(10):2789-2800. · 2.24 Impact Factor
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  Available from: Thomas Murray

  Article: Biosynthetically intriguing chlorinated lipophilic metabolites from geographically distant tropical marine cyanobacteria.

  Joshawna K Nunnery, Niclas Engene, Tara Byrum, Zhengyu Cao, Sairam V Jabba, Alban R Pereira, Teatulohi Matainaho, Thomas F Murray, William H Gerwick
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  ABSTRACT: Five new vinylchlorine-containing metabolites, the lipoamides janthielamide A and kimbeamides A-C and the ketide-extended pyranone kimbelactone A, have been isolated from collections of marine cyanobacteria made in Curaçao and Papua New Guinea. Both janthielamide A and kimbeamide A exhibited moderate sodium channel blocking activity in murine Neuro-2a cells. Consistent with this activity, janthielamide A was also found to antagonize veratridine-induced sodium influx in murine cerebrocortical neurons. These lipoamides represent the newest additions to a relatively rare family of marine cyanobacterial-derived lipoamides and a new structural class of compounds exhibiting neuromodulatory activities from marine cyanobacteria.
  The Journal of Organic Chemistry 04/2012; 77(9):4198-208. · 4.45 Impact Factor
• Article: Antifungal Depsidone Metabolites from Cordyceps dipterigena, an Endophytic Fungus Antagonistic to the Phytopathogen Gibberella fujikuroi.

  Titto Varughese, Nivia Riosa, Sarah Higginbotham, A Elizabeth Arnold, Phyllis D Coley, Thomas A Kursar, William H Gerwick, L Cubilla Rios
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  ABSTRACT: Among thirty four endophytic fungal strains screened for in vitro antagonism, the endophytic fungus Cordyceps dipterigena was found to strongly inhibit mycelial growth of the plant pathogenic fungus Gibberella fujikuroi. Two new depsidone metabolites, cordycepsidone A (1) and cordycepsidone B (2), were isolated from the PDA culture extract of C. dipterigena and identified as being responsible for the antifungal activity. Elucidation of their chemical structures was carried out using 1D and 2D NMR spectroscopy in combination with IR and MS spectroscopic data. Cordycepsidone A displayed strong and dose-dependent antifungal activity against the plant pathogenic fungus Gibberella fujikuroi. The isolates were inactive in bioassays for malaria (Plasmodium falciparum), leishmaniasis (Leishmania donovani), Chagas's disease (Trypanosoma cruzi), and cytotoxicity at 10 μg/mL. The compounds were also found to be inactive against several bacterial strains at 50 μg/mL.
  Tetrahedron Letters 03/2012; 53(13):1624-1626. · 2.68 Impact Factor
• Article: The carmaphycins: new proteasome inhibitors exhibiting an α,β-epoxyketone warhead from a marine cyanobacterium.

  Alban R Pereira, Andrew J Kale, Andrew T Fenley, Tara Byrum, Hosana M Debonsi, Michael K Gilson, Frederick A Valeriote, Bradley S Moore, William H Gerwick
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  ABSTRACT: Two new peptidic proteasome inhibitors were isolated as trace components from a Curaçao collection of the marine cyanobacterium Symploca sp. Carmaphycin A (1) and carmaphycin B (2) feature a leucine-derived α,β-epoxyketone warhead directly connected to either methionine sulfoxide or methionine sulfone. Their structures were elucidated on the basis of extensive NMR and MS analyses and confirmed by total synthesis, which in turn provided more material for further biological evaluations. Pure carmaphycins A and B were found to inhibit the β5 subunit (chymotrypsin-like activity) of the S. cerevisiae 20S proteasome in the low nanomolar range. Additionally, they exhibited strong cytotoxicity to lung and colon cancer cell lines, as well as exquisite antiproliferative effects in the NCI60 cell-line panel. These assay results as well as initial structural biology studies suggest a distinctive binding mode for these new inhibitors.
  ChemBioChem 03/2012; 13(6):810-7. · 3.94 Impact Factor
• Article: The chemical ecology of cyanobacteria.

  Pedro N Leão, Niclas Engene, Agostinho Antunes, William H Gerwick, Vitor Vasconcelos
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  ABSTRACT: This review covers the literature on the chemically mediated ecology of cyanobacteria, including ultraviolet radiation protection, feeding-deterrence, allelopathy, resource competition, and signalling. To highlight the chemical and biological diversity of this group of organisms, evolutionary and chemotaxonomical studies are presented. Several technologically relevant aspects of cyanobacterial chemical ecology are also discussed.
  Natural Product Reports 02/2012; 29(3):372-91. · 9.79 Impact Factor
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  Available from: Lena Gerwick

  Article: Evaluation of Streptomyces coelicolor A3(2) as a heterologous expression host for the cyanobacterial protein kinase C activator lyngbyatoxin A.

  Adam C Jones, Sabine Ottilie, Alessandra S Eustáquio, Daniel J Edwards, Lena Gerwick, Bradley S Moore, William H Gerwick
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  ABSTRACT: Filamentous marine cyanobacteria are extremely rich sources of bioactive natural products and often employ highly unusual biosynthetic enzymes in their assembly. However, the current lack of techniques for stable DNA transfer into these filamentous organisms, combined with the absence of heterologous expression strategies for nonribosomal cyanobacterial gene clusters, prohibit the creation of mutant strains or the heterologous production of these cyanobacterial compounds in other bacteria. In this study, we evaluated the capability of a derivative of the model actinomycete Streptomyces coelicolor A3(2) to express enzymes involved in the biosynthesis of the protein kinase C activator lyngbyatoxin A from a Hawaiian strain of Moorea producta (previously classified as Lyngbya majuscula). Despite large differences in GC content between these two bacteria and the presence of rare TTA/UUA leucine codons in lyngbyatoxin ORFs we were able to achieve expression of the cytochrome P450 monooxygenase LtxB and reverse prenyltransferase LtxC in S. coelicolor M512 and confirmed the in vitro functionality of S. coelicolor overexpressed LtxC. Attempts to express the entire lyngbyatoxin A gene cluster in S. coelicolor M512 were not successful because of transcript termination observed for the ltxA gene, which encodes a large nonribosomal peptide synthetase. However, these attempts did show a detectable level of cyanobacterial promoter recognition in Streptomyces. Successful expression of lyngbyatoxin A proteins in Streptomyces provides a new platform for biochemical investigation of natural product enzymes from Moorea strains.
  FEBS Journal 02/2012; 279(7):1243-51. · 3.79 Impact Factor
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  Available from: Carmenza Spadafora

  Article: Antiparasitic and anticancer constituents of the endophytic fungus Aspergillus sp. strain F1544.

  Sergio Martínez-Luis, Lilia Cherigo, Elizabeth Arnold, Carmenza Spadafora, William H Gerwick, Luis Cubilla-Rios
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  ABSTRACT: With the combined goal of finding the best anti-parasitic and anti-cancer activities as well as isolating the bioactive agents and studying their structures and biological properties, we proceeded to perform a small-scale cultivation of Aspergillus sp. strain F1544 using Potato Dextrose, Malt Extract, Czapek Dox and Eight Vegetables media. From the more promising extracts (obtaining using potato dextrose and czapek dox media in large scale) of this fungus, we isolated the five compounds: pseurotin A (1), 14-norpseurotin A (2), FD-838 (3), and pseurotin D (4), and fumoquinone B (5). All compounds showed good antileishmanial and moderate anticancer activities.
  Natural product communications 02/2012; 7(2):165-8. · 1.24 Impact Factor
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  Available from: Carmenza Spadafora

  Article: Coibanoles, a new class of meroterpenoids produced by Pycnoporus sanguineus

  Eunice Molinar, Nivia Rios, Carmenza Spadafora, A. Elizabeth Arnold, Phyllis D. Coley, Thomas A. Kursar, William H. Gerwick, Luis Cubilla-Rios
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  ABSTRACT: Three new terpenoids of mixed biosynthetic origin were isolated from the culture filtrate of the endophytic fungus Pycnoporus sanguineus. Their structures were determined by extensive spectroscopic analyses. We have named these tricyclic and tetracyclic metabolites ‘coibanoles A–C’ in reference to Coiba Island and Coiba National Park, Panamá, from which the plant and endophyte were collected. The extract was inactive to the human parasites Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum at a test concentration of 10 μg/mL.
  Tetrahedron Letters 02/2012; 53(8-ISSN: 0040-4039):919-922. · 2.68 Impact Factor