@article{AbdelmohsenChengViegelmannetal.2014,
  author    = {Abdelmohsen, Usama Ramadan and Cheng, Cheng and Viegelmann, Christina and Zhang, Tong and Grkovic, Tanja and Ahmed, Safwat and Quinn, Ronald J. and Hentschel, Ute and Edrada-Ebel, RuAngelie},
  title     = {Dereplication Strategies for Targeted Isolation of New Antitrypanosomal Actinosporins A and B from a Marine Sponge Associated-Actinokineospora sp EG49},
  series = {Marine Drugs},
  volume    = {12},
  journal   = {Marine Drugs},
  number    = {3},
  issn      = {1660-3397},
  doi       = {10.3390/md12031220},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119876},
  pages     = {1220-44},
  year      = {2014},
  abstract  = {High resolution Fourier transform mass spectrometry (HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy were employed as complementary metabolomic tools to dereplicate the chemical profile of the new and antitrypanosomally active sponge-associated bacterium Actinokineospora sp. EG49 extract. Principal Component (PCA), hierarchical clustering (HCA), and orthogonal partial least square-discriminant analysis (OPLS-DA) were used to evaluate the HRFTMS and NMR data of crude extracts from four different fermentation approaches. Statistical analysis identified the best culture one-strain-many-compounds (OSMAC) condition and extraction procedure, which was used for the isolation of novel bioactive metabolites. As a result, two new O-glycosylated angucyclines, named actinosporins A (1) and B (2), were isolated from the broth culture of Actinokineospora sp. strain EG49, which was cultivated from the Red Sea sponge Spheciospongia vagabunda. The structures of actinosporins A and B were determined by 1D- and 2D-NMR techniques, as well as high resolution tandem mass spectrometry. Testing for antiparasitic properties showed that actinosporin A exhibited activity against Trypanosoma brucei brucei with an IC₅₀ value of 15 µM; however no activity was detected against Leishmania major and Plasmodium falciparum, therefore suggesting its selectivity against the parasite Trypanosoma brucei brucei; the causative agent of sleeping sickness.},
  language  = {en}
}
@article{DashtiGrkovicAbdelmohsenetal.2014,
  author    = {Dashti, Yousef and Grkovic, Tanja and Abdelmohsen, Usama Ramadan and Hentschel, Ute and Quinn, Ronald J.},
  title     = {Production of Induced Secondary Metabolites by a Co-Culture of Sponge-Associated Actinomycetes, Actinokineospora sp EG49 and Nocardiopsis sp RV163},
  series = {MARINE DRUGS},
  volume    = {12},
  journal   = {MARINE DRUGS},
  number    = {5},
  issn      = {1660-3397},
  doi       = {10.3390/md12053046},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116547},
  pages     = {3046-3059},
  year      = {2014},
  abstract  = {Two sponge-derived actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163, were grown in co-culture and the presence of induced metabolites monitored by H-1 NMR. Ten known compounds, including angucycline, diketopiperazine and beta-carboline derivatives 1-10, were isolated from the EtOAc extracts of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Co-cultivation of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163 induced the biosynthesis of three natural products that were not detected in the single culture of either microorganism, namely N-(2-hydroxyphenyl)-acetamide (11), 1,6-dihydroxyphenazine (12) and 5a, 6,11a, 12-tetrahydro-5a, 11a-dimethyl[1,4]benzoxazino[3,2-b][1,4]benzoxazine (13a). When tested for biological activity against a range of bacteria and parasites, only the phenazine 12 was active against Bacillus sp. P25, Trypanosoma brucei and interestingly, against Actinokineospora sp. EG49. These findings highlight the co-cultivation approach as an effective strategy to access the bioactive secondary metabolites hidden in the genomes of marine actinomycetes.},
  language  = {en}
}
@article{OliAbdelmohsenHentscheletal.2014,
  author    = {Oli, Swarna and Abdelmohsen, Usama Ramadan and Hentschel, Ute and Schirmeister, Tanja},
  title     = {Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Fractionation},
  series = {MARINE DRUGS},
  volume    = {12},
  journal   = {MARINE DRUGS},
  number    = {5},
  issn      = {1660-3397},
  doi       = {10.3390/md12052614},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116536},
  pages     = {2614-2622},
  year      = {2014},
  abstract  = {In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC50 value of 5 mu M and without cytotoxic effects against J774.1 macrophages at 100 mu M concentration. Plakortide E was isolated from the sponge Plakortis halichondroides using enzyme assay-guided fractionation and identified by NMR spectroscopy and mass spectrometry. Furthermore, enzyme kinetic studies confirmed plakortide E as a non-competitive, slowly-binding, reversible inhibitor of rhodesain.},
  language  = {en}
}
@article{MacintyreZhangViegelmannetal.2014,
  author    = {Macintyre, Lynsey and Zhang, Tong and Viegelmann, Christina and Martinez, Ignacio Juarez and Cheng, Cheng and Dowdells, Catherine and Abdelmohsen, Usama Ramadan and Gernert, Christine and Hentschel, Ute and Edrada-Ebel, RuAngelie},
  title     = {Metabolomic Tools for Secondary Metabolite Discovery from Marine Microbial Symbionts},
  series = {Marine Drugs},
  volume    = {12},
  journal   = {Marine Drugs},
  number    = {6},
  issn      = {1660-3397},
  doi       = {10.3390/md12063416},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116097},
  pages     = {3416-3448},
  year      = {2014},
  abstract  = {Marine invertebrate-associated symbiotic bacteria produce a plethora of novel secondary metabolites which may be structurally unique with interesting pharmacological properties. Selection of strains usually relies on literature searching, genetic screening and bioactivity results, often without considering the chemical novelty and abundance of secondary metabolites being produced by the microorganism until the time-consuming bioassay-guided isolation stages. To fast track the selection process, metabolomic tools were used to aid strain selection by investigating differences in the chemical profiles of 77 bacterial extracts isolated from cold water marine invertebrates from Orkney, Scotland using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Following mass spectrometric analysis and dereplication using an Excel macro developed in-house, principal component analysis (PCA) was employed to differentiate the bacterial strains based on their chemical profiles. NMR H-1 and correlation spectroscopy (COSY) were also employed to obtain a chemical fingerprint of each bacterial strain and to confirm the presence of functional groups and spin systems. These results were then combined with taxonomic identification and bioassay screening data to identify three bacterial strains, namely Bacillus sp. 4117, Rhodococcus sp. ZS402 and Vibrio splendidus strain LGP32, to prioritize for scale-up based on their chemically interesting secondary metabolomes, established through dereplication and interesting bioactivities, determined from bioassay screening.},
  language  = {en}
}
@article{AbdelmohsenYangHornetal.2014,
  author    = {Abdelmohsen, Usama Ramadan and Yang, Chen and Horn, Hannes and Hajjar, Dina and Ravasi, Timothy and Hentschel, Ute},
  title     = {Actinomycetes from Red Sea Sponges: Sources for Chemical and Phylogenetic Diversity},
  doi       = {10.3390/md12052771},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112882},
  year      = {2014},
  abstract  = {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.},
  subject      = {Meeresschw{\"a}mme},
  language  = {en}
}
@article{HarjesRyuAbdelmohsenetal.2014,
  author    = {Harjes, Janno and Ryu, Taewoo and Abdelmohsen, Usama Ramadan and Moitinho-Silva, Lucas and Horn, Hannes and Ravasi, Timothy and Hentschel, Ute},
  title     = {Draft Genome Sequence of the Antitrypanosomally Active Sponge-Associated Bacterium Actinokineospora sp. Strain EG49},
  doi       = {10.1128/genomeA.00160-14},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112776},
  year      = {2014},
  abstract  = {The marine sponge-associated bacterium Actinokineospora sp. strain EG49 produces the antitrypanosomal angucycline-like compound actinosporin A. The draft genome of Actinokineospora sp. EG49 has a size of 7.5 megabases and a GC content of 72.8\% and contains 6,629 protein-coding sequences (CDS). antiSMASH predicted 996 genes residing in 36 secondary metabolite gene clusters.},
  subject      = {Strahlenpilze},
  language  = {en}
}
@article{HentschelKamkeRinkeetal.2014,
  author    = {Hentschel, Ute and Kamke, Janine and Rinke, Christian and Schwientek, Patrick and Mavromatis, Kostas Mavromatis and Ivanova, Natalia and Sczyrba, Alexander and Woyke, Tanja},
  title     = {The Candidate Phylum Poribacteria by Single-Cell Genomics: New Insights into Phylogeny, Cell-Compartmentation, Eukaryote-Like Repeat Proteins, and Other Genomic Features},
  doi       = {10.1371/journal.pone.0087353},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112649},
  year      = {2014},
  abstract  = {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.},
  language  = {en}
}