TY - JOUR A1 - Cheng, Cheng A1 - Othman, Eman M. A1 - Stopper, Helga A1 - Edrada-Ebel, RuAngelie A1 - Hentschel, Ute A1 - Abdelmohsen, Usama Ramadan T1 - Isolation of petrocidin A, a new cytotoxic cyclic dipeptide from the marine sponge-derived bacterium \(Streptomyces\) sp. SBT348 JF - Marine Drugs N2 - A new cyclic dipeptide, petrocidin A (\(\textbf{1}\)), along with three known compounds—2,3-dihydroxybenzoic acid (\(\textbf{2}\)), 2,3-dihydroxybenzamide (\(\textbf{3}\)), and maltol (\(\textbf{4}\))—were isolated from the solid culture of \(Streptomyces\) sp. SBT348. The strain \(Streptomyces\) sp. SBT348 had been prioritized in a strain collection of 64 sponge-associated actinomycetes based on its distinct metabolomic profile using liquid chromatography/high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). The absolute configuration of all α-amino acids was determined by HPLC analysis after derivatization with Marfey’s reagent and comparison with commercially available reference amino acids. Structure elucidation was pursued in the presented study by mass spectrometry and NMR spectral data. Petrocidin A (\(\textbf{1}\)) and 2,3-dihydroxybenzamide (\(\textbf{3}\)) exhibited significant cytotoxicity towards the human promyelocytic HL-60 and the human colon adenocarcinoma HT-29 cell lines. These results demonstrated the potential of sponge-associated actinomycetes for the discovery of novel and pharmacologically active natural products. KW - biology KW - sponges KW - actinomycetes KW - streptomyces KW - cyclic dipeptide KW - cytotoxic Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172644 VL - 15 IS - 12 ER - TY - JOUR A1 - Cheng, Cheng A1 - MacIntyre, Lynsey A1 - Ramadan Abdelmohsen, Usama A1 - Horn, Hannes A1 - Polymenakou, Paraskevi N. A1 - Edrada-Ebel, RuAngelie A1 - Hentschel, Ute T1 - Biodiversity, Anti-Trypanosomal Activity Screening, and Metabolomic Profiling of Actinomycetes Isolated from Mediterranean Sponges JF - PLoS One N2 - Marine sponge–associated actinomycetes are considered as promising sources for the discovery of novel biologically active compounds. In the present study, a total of 64 actinomycetes were isolated from 12 different marine sponge species that had been collected offshore the islands of Milos and Crete, Greece, eastern Mediterranean. The isolates were affiliated to 23 genera representing 8 different suborders based on nearly full length 16S rRNA gene sequencing. Four putatively novel species belonging to genera Geodermatophilus, Microlunatus, Rhodococcus and Actinomycetospora were identified based on a 16S rRNA gene sequence similarity of < 98.5% to currently described strains. Eight actinomycete isolates showed bioactivities against Trypanosma brucei brucei TC221 with half maximal inhibitory concentration (IC50) values <20 μg/mL. Thirty four isolates from the Milos collection and 12 isolates from the Crete collection were subjected to metabolomic analysis using high resolution LC-MS and NMR for dereplication purposes. Two isolates belonging to the genera Streptomyces (SBT348) and Micromonospora (SBT687) were prioritized based on their distinct chemistry profiles as well as their anti-trypanosomal activities. These findings demonstrated the feasibility and efficacy of utilizing metabolomics tools to prioritize chemically unique strains from microorganism collections and further highlight sponges as rich source for novel and bioactive actinomycetes. KW - streptomyces KW - drug metabolism KW - metabolites KW - ribosomal RNA KW - metabolomics KW - actinobacteria KW - sponges KW - secondary metabolites Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125138 VL - 10 IS - 9 ER - TY - JOUR A1 - Abdelmohsen, Usama Ramadan A1 - Yang, Chen A1 - Horn, Hannes A1 - Hajjar, Dina A1 - Ravasi, Timothy A1 - Hentschel, Ute T1 - Actinomycetes from Red Sea Sponges: Sources for Chemical and Phylogenetic Diversity N2 - The diversity of actinomycetes associated with marine sponges collected off Fsar Reef (Saudi Arabia) was investigated in the present study. Forty-seven actinomycetes were cultivated and phylogenetically identified based on 16S rRNA gene sequencing and were assigned to 10 different actinomycete genera. Eight putatively novel species belonging to genera Kocuria, Mycobacterium, Nocardia, and Rhodococcus were identified based on sequence similarity values below 98.2% to other 16S rRNA gene sequences available in the NCBI database. PCR-based screening for biosynthetic genes including type I and type II polyketide synthases (PKS-I, PKS-II) as well as nonribosomal peptide synthetases (NRPS) showed that 20 actinomycete isolates encoded each at least one type of biosynthetic gene. The organic extracts of nine isolates displayed bioactivity against at least one of the test pathogens, which were Gram-positive and Gram-negative bacteria, fungi, human parasites, as well as in a West Nile Virus protease enzymatic assay. These results emphasize that marine sponges are a prolific resource for novel bioactive actinomycetes with potential for drug discovery. KW - PKS I KW - Meeresschwämme KW - PKS II KW - NRPS KW - Red sea KW - sponges KW - actinomycetes KW - bioactivity Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112882 ER - TY - JOUR A1 - Hentschel, Ute A1 - Kamke, Janine A1 - Rinke, Christian A1 - Schwientek, Patrick A1 - Mavromatis, Kostas Mavromatis A1 - Ivanova, Natalia A1 - Sczyrba, Alexander A1 - Woyke, Tanja T1 - The Candidate Phylum Poribacteria by Single-Cell Genomics: New Insights into Phylogeny, Cell-Compartmentation, Eukaryote-Like Repeat Proteins, and Other Genomic Features N2 - The candidate phylum Poribacteria is one of the most dominant and widespread members of the microbial communities residing within marine sponges. Cell compartmentalization had been postulated along with their discovery about a decade ago and their phylogenetic association to the Planctomycetes, Verrucomicrobia, Chlamydiae superphylum was proposed soon thereafter. In the present study we revised these features based on genomic data obtained from six poribacterial single cells. We propose that Poribacteria form a distinct monophyletic phylum contiguous to the PVC superphylum together with other candidate phyla. Our genomic analyses supported the possibility of cell compartmentalization in form of bacterial microcompartments. Further analyses of eukaryote-like protein domains stressed the importance of such proteins with features including tetratricopeptide repeats, leucin rich repeats as well as low density lipoproteins receptor repeats, the latter of which are reported here for the first time from a sponge symbiont. Finally, examining the most abundant protein domain family on poribacterial genomes revealed diverse phyH family proteins, some of which may be related to dissolved organic posphorus uptake. KW - Candidate Phylum Poribacteria KW - protein domains KW - genomic databases KW - phylogenetic analysis KW - genome analysis KW - sponges KW - marine bacteria KW - phylogenetics KW - polyvinyl chloride Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112649 N1 - This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. ER - TY - THES A1 - Jadulco, Raquel C. T1 - Isolation and structure elucidation of bioactive secondary metabolites from marine sponges and sponge-derived fungi T1 - Isolierung und strukturelle Identifizierung von biologisch aktiven Naturstoffen aus marinen Schwämme und aus Schwämmen isolierte Pile N2 - Low-molecular mass natural products from bacteria, fungi, plants and marine organisms exhibit unique structural diversity which are of interest for the identification of new lead structures for medicinals and agrochemicals. In the search for bioactive compounds from marine sponges and sponge-associated fungi, this research work resulted to the isolation of twenty-six compounds, eight of which are new metabolites. The sponges were collected from the Indo-pacific regions, particularly those from Indonesian and Philippine waters, as well as those from the Mediterranean Sea near the island of Elba in Italy. A combination of the chemically- and biologically-driven approach for drug discovery was employed, wherein extracts were screened for antibacterial, antifungal and cytotoxic activities. In addition to the bioassay-guided approach to purify the compounds responsible for the activity of the extract, TLC, UV and MS were also used to isolate the chemically most interesting substances. Hence, purified compounds which are not responsible for the initial bioscreening activity may have a chance to be evaluated for other bioactivities. Enumerated below are the compounds which have been isolated and structurally elucidated and whose bioactivities have been further characterized. 1. The extract of the fungus Cladosporium herbarum associated with the sponge Callyspongia aerizusa afforded seven structurally related polyketides, including two new twelve-membered macrolides: pandangolide 3 and 4, and a new acetyl congener of the previously isolated 5-hydroxymethyl-2-furoic acid. The two furoic acid analogues isolated were found to be responsible for the antimicrobial activity of the extract. The isolation of the known phytotoxin Cladospolide B from Cladosporium herbarum, which was originally known from Cladosporium cladosporioides and C. tenuissimum, indicates the possibility that Cladospolide B may be a chemotaxonomic marker of particular Cladosporium species. 2. The extract of the fungus Curvularia lunata associated with the Indonesian sponge Niphates olemda yielded three compounds, namely the new antimicrobially-active anthraquinone lunatin, the known bisanthraquinone cytoskyrin A, and the known plant hormone abscisic acid. The co-occurrence of the two structurally-related anthraquinones suggests that the monomeric lunatin may be a precursor in the biosynthesis of the bisanthraquinone cytoskyrin A. 3. The fungus Penicillium spp. associated with the Mediterranean sponge Axinella verrucosa yielded six compounds, namely the known antifungal griseofulvin and its less active dechloro analogue; the known toxin oxaline; and the known cytotoxic metabolite communesin B and its two new congeners communesin C and D. The new communesins were less active than communesin B in the brine-shrimp lethality test. 4. An unidentified fungus which was also isolated from the same Mediterranean sponge Axinella verrucosa as Penicillium spp. yielded the known compound monocerin which has been reported to possess phytotoxic and insecticidal activities. 5. The fungus Aspergillus flavus associated with the Philippine sponge Hyrtios aff. reticulatus yielded the known toxin a-cyclopiazonic acid. 6. The Indonesian sponge Agelas nakamurai yielded four bromopyrrole alkaloids namely the new compound 4-bromo-pyrrole-2-carboxylic acid, and the known compounds: 4-bromo-pyrrole-2-carboxamide, mukanadin B and mukanadin C. All of the four compounds except mukanadin B were found to be antimicrobially-active. Bromopyrrole alkaloids are well-known metabolites of the genus Agelas and are proven to play an important role in the chemical defense of the sponge against predation from fishes. 7. The Indonesian sponge Jaspis splendens yielded three known substances which are known for their antiproliferative activities, namely the depsipeptides jaspamide (jasplakinolide), and its derivatives jaspamide B and jaspamide C. N2 - Niedermolekulare Naturstoffe aus Bakterien, Pilzen, Pflanzen und marinen Organismen weisen eine einzigartige strukturelle Diversität auf, die für die Identifizierung neuer Leitstrukturen für die Entwicklung von Arzneistoffen und Pflanzenschutzmitteln von großer Bedeutung ist. Im Rahmen der Suche nach bioaktiven Verbindungen aus marinen Schwämmen und mit diesen Schwämmen assoziierten Pilzen wurden in dieser Arbeit insgesamt 26 Sekundärstoffe isoliert, wobei es sich bei acht Substanzen um neue Verbindungen handelt. Die Schwämme wurden im indo-pazifischen Gebiet gesammelt, insbesondere aus Indonesien und den Philippinen, so wie aus dem Mittelmeer in der Nähe der Insel Elba in Italien. Für die Entdeckung neuer bioaktiver Substanzen wurde eine Kombination von chemischen und biologischen Methoden angewendet, wodurch Extrakte mit verschiedenen Screening-Methoden auf Bioaktivität getestet worden sind. Zum Einsatz kamen dabei Versuche mit Raupen des polyphagen Nachtfalters Spodoptera littoralis (Noctuidae; Lepidoptera) im Hinblick auf potentielle insektizide Wirkungen, antimikrobielle Untersuchungen mit gram-negativen und gram-positiven Bakterien und dem Pilz Candida albicans, Zytotoxizitätstests gegenüber menschlichen Krebszellen und Toxizitätstests mit dem Krebs Artemia salina. Zusätzlich zur bioaktivitäts-geleiteten Isolierung von Substanzen aus aktiven Extrakten wurden daneben auch DC, UV und MS als Kriterien herangezogen, um die aus chemischer Sicht interessantesten Verbindungen zu isolieren. Damit konnten auch solche Substanzen, die nicht für die Aktivität der Extrakte im Bioscreening verantwortlich waren, weiteren Biotests unterzogen werden. Im einzelnen wurden die folgenden Verbindungen isoliert, ihre Struktur aufgeklärt, und ihre biologische Aktivität näher charakterisiert: 1. Der antimikrobiell aktive Extrakt aus dem Pilz Cladosporium herbarum, der mit dem indonesischen Schwamm Callyspongia aerizusa assoziiert ist, ergab sieben Polyketide, die strukturell ähnlich sind, einschließlich der beiden neuen zwölf-gliedrigen Makrolide Pandangolid 3 und Pandangolid 4, sowie ein neues acetyliertes Derivat des bereits bekannten Naturstoffs 5-Hyroxymethyl-2-furancarbonsäure. Beide Furancarbonsäuren zeigten antimikrobielle Aktivität und dürften deshalb hauptsächlich für die antimikrobielle Aktivität des Extrakts verantwortlich sein. Daß Cladospolid B, ein bekanntes Phytotoxin, das bereits für die Arten Cladosporium cladosporoiodes und C. tenuissimum beschrieben wurde, ebenfalls aus C. herbarum isoliert wurde, deutet darauf hin, daß Cladospolid B als ein chemotaxonomischer Marker für bestimmte Cladosporium-Arten angesehen werden könnte. 2. Der antimikrobiell aktive Extrakt aus dem Pilz Curvularia lunata, der mit dem indonesischen Schwamm Niphates olemda assoziiert ist, ergab drei Substanzen, nämlich das neue antimikrobiell aktive Anthrachinon Lunatin sowie das bereits bekannte Bisanthrachinon Cytoskyrin A, und das bekannte Pflanzenhormon Abscisinsäure. Das gemeinsame Vorkommen der beiden strukturell verwandten Anthranoide könnte ein Indiz dafür sein, daß das Monomer Lunatin eine biogenetische Vorstufe des Bisanthrachinons Cytoskyrin A darstellt. 3. Ein mit dem im Mittelmeer gesammelten Schwamm Axinella verrucosa assoziierter Pilz der Gattung Penicillium ergab insgesamt sechs Substanzen, im einzelnen das bekannte Antimykotikum Griseofulvin und dessen weniger aktives Dechlor-Derivat, das bekannte Toxin Oxalin, sowie die als zytotoxisch beschriebene Verbindung Communesin B und deren neue Derivate Communesin C und Communesin D. Im Vergleich zu Communesin B erwiesen sich die neuen Communesin-Derivate als weniger aktiv gegenüber dem Krebs A. salina. 4. Ein bisher unidentifizierter Pilz aus dem gleichen Schwamm Axinella verrucosa lieferte die bekannte Substanz Monocerin, über deren phytotoxische und insektizide Eigenschaften bereits berichtet wurde. 5. Der mit dem philippinischen Schwamm Hyrtios aff. reticulatus assoziierte Pilz Aspergillus flavus ergab das bereits bekannte Toxin a-Cyclopiazonsäure. 6. Der indonesische Schwamm Agelas nakamurai lieferte vier bromierte Pyrrol-Alkaloide, nämlich die neue Substanz 4-Brompyrrol-2-carbonsäure sowie die bereits bekannten Verbindungen 4-Brompyrrol-2-carboxamid, Mukanadin B und Mukanadin C. Alle vier Substanzen außer Mukanadin B zeigten antimikrobielle Aktivität. Bromierte Pyrrol-Alkaloide wurden in vielen Untersuchungen als typische Sekundärstoffe der Schwammgattung Agelas beschrieben, die bei der chemischen Verteidigung der Schwämme gegen Fische eine wichtige Rolle spielen. 7. Der indonesiche Schwamm Jaspis splendens ergab drei bekannte Substanzen, die für ihre antiproliferative Aktivität bekannt sind, nämlich die Depsipeptide Jaspamid (Jasplakinolid) und dessen Derivate Jaspamid B und Jaspamid C. KW - Meeresschwämme KW - Pilze KW - Sekundärmetabolit KW - Marin KW - Schwämme KW - Pilze KW - Naturstoff KW - Marine KW - sponges KW - fungi KW - metabolites Y1 - 2002 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-3565 ER -