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  - Pimentel-Elardo, Sheila Marie
A1  - Kozytska, Svitlana
A1  - Bugni, Tim S.
A1  - Ireland, Chris M.
A1  - Moll, Heidrun
A1  - Hentschel, Ute
T1  - Anti-Parasitic Compounds from Streptomyces sp. Strains Isolated from Mediterranean Sponges
N2  - Actinomycetes are prolific producers of pharmacologically important compounds accounting for about 70% of the naturally derived antibiotics that are currently in clinical use. In this study, we report on the isolation of Streptomyces sp. strains from Mediterranean sponges, on their secondary metabolite production and on their screening for anti-infective activities. Bioassay-guided isolation and purification yielded three previously known compounds namely, cyclic depsipeptide valinomycin, indolocarbazole alkaloid staurosporine and butenolide. This is the first report of the isolation of valinomycin from a marine source. These compounds exhibited novel anti-parasitic activities specifically against Leishmania major (valinomycin IC50 < 0.11 μM; staurosporine IC50 5.30 μM) and Trypanosoma brucei brucei (valinomycin IC50 0.0032 μM; staurosporine IC50 0.022 μM; butenolide IC50 31.77 μM). These results underscore the potential of marine actinomycetes to produce bioactive compounds as well as the re-evaluation of previously known compounds for novel anti-infective activities.
KW  - Biologie
KW  - marine sponges
KW  - Streptomyces
KW  - valinomycin
KW  - staurosporine
KW  - butenolide
KW  - anti-parasitic
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68312
ER  - 
TY  - JOUR
A1  - Abdelmohsen, Usama Ramadan
A1  - Szesny, Matthias
A1  - Othman, Eman Maher
A1  - Schirmeister, Tanja
A1  - Grond, Stepanie
A1  - Stopper, Helga
A1  - Hentschel, Ute
T1  - Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115
N2  - Diazepinomicin is a dibenzodiazepine alkaloid with an unusual structure among the known microbial metabolites discovered so far. Diazepinomicin was isolated from the marine sponge-associated strain Micromonospora sp. RV115 and was identified by spectroscopic analysis and by comparison to literature data. In addition to its interesting preclinical broad-spectrum antitumor potential, we report here new antioxidant and anti-protease activities for this compound. Using the ferric reducing antioxidant power (FRAP) assay, a strong antioxidant potential of diazepinomicin was demonstrated. Moreover, diazepinomicin showed a significant antioxidant and protective capacity from genomic damage induced by the reactive oxygen species hydrogen peroxide in human kidney (HK-2) and human promyelocytic (HL-60) cell lines. Additionally, diazepinomicin inhibited the proteases rhodesain and cathepsin L at an IC50 of 70–90 μM. It also showed antiparasitic activity against trypomastigote forms of Trypanosoma brucei with an IC50 of 13.5 μM. These results showed unprecedented antioxidant and anti-protease activities of diazepinomicin, thus further highlighting its potential as a future drug candidate.
KW  - Biologie
KW  - diazepinomicin
KW  - anti-protease
KW  - antioxidant
KW  - actinomycetes
KW  - Micromonospora
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76279
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  - Cheng, Cheng
A1  - Viegelmann, Christina
A1  - Zhang, Tong
A1  - Grkovic, Tanja
A1  - Ahmed, Safwat
A1  - Quinn, Ronald J.
A1  - Hentschel, Ute
A1  - Edrada-Ebel, RuAngelie
T1  - Dereplication Strategies for Targeted Isolation of New Antitrypanosomal Actinosporins A and B from a Marine Sponge Associated-Actinokineospora sp EG49
JF  - Marine Drugs
N2  - 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.
KW  - dereplication
KW  - secondary metabolomics
KW  - anti-trypanosoma
KW  - Actinokineospora
KW  - Spheciospongia vagabunda
KW  - actinosporins
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119876
SN  - 1660-3397
VL  - 12
IS  - 3
ER  - 
TY  - JOUR
A1  - Pimentel-Elardo, Sheila Marie
A1  - Grozdanov, Lubomir
A1  - Proksch, Sebastian
A1  - Hentschel, Ute
T1  - Diversity of Nonribosomal Peptide Synthetase Genes in the Microbial Metagenomes of Marine Sponges
N2  - Genomic mining revealed one major nonribosomal peptide synthetase (NRPS) phylogenetic cluster in 12 marine sponge species, one ascidian, an actinobacterial isolate and seawater. Phylogenetic analysis predicts its taxonomic affiliation to the actinomycetes and hydroxy-phenyl-glycine as a likely substrate. Additionally, a phylogenetically distinct NRPS gene cluster was discovered in the microbial metagenome of the sponge Aplysina aerophoba, which shows highest similarities to NRPS genes that were previously assigned, by ways of single cell genomics, to a Chloroflexi sponge symbiont. Genomic mining studies such as the one presented here for NRPS genes, contribute to on-going efforts to characterize the genomic potential of sponge-associated microbiota for secondary metabolite biosynthesis.
KW  - Biologie
KW  - nonribosomal peptide synthetase
KW  - NRPS
KW  - marine sponge
KW  - Porifera
KW  - metagenomics
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75990
ER  - 
TY  - JOUR
A1  - Horn, Hannes
A1  - Keller, Alexander
A1  - Hildebrandt, Ulrich
A1  - Kämpfer, Peter
A1  - Riederer, Markus
A1  - Hentschel, Ute
T1  - Draft genome of the \(Arabidopsis\) \(thaliana\) phyllosphere bacterium, \(Williamsia\) sp. ARP1
JF  - Standards in Genomic Sciences
N2  - The Gram-positive actinomycete \(Williamsia\) sp. ARP1 was originally isolated from the \(Arabidopsis\) \(thaliana\) phyllosphere. Here we describe the general physiological features of this microorganism together with the draft genome sequence and annotation. The 4,745,080 bp long genome contains 4434 protein-coding genes and 70 RNA genes. To our knowledge, this is only the second reported genome from the genus \(Williamsia\) and the first sequenced strain from the phyllosphere. The presented genomic information is interpreted in the context of an adaptation to the phyllosphere habitat.
KW  - arabidopsis thaliana
KW  - whole genome sequencing
KW  - adaption
KW  - Williamsia sp. ARP1
KW  - phyllosphere
KW  - draft genome
KW  - next generation sequencing
KW  - assembly
KW  - annotation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146008
VL  - 11
IS  - 8
ER  - 
TY  - JOUR
A1  - Harjes, Janno
A1  - Ryu, Taewoo
A1  - Abdelmohsen, Usama Ramadan
A1  - Moitinho-Silva, Lucas
A1  - Horn, Hannes
A1  - Ravasi, Timothy
A1  - Hentschel, Ute
T1  - Draft Genome Sequence of the Antitrypanosomally Active Sponge-Associated Bacterium Actinokineospora sp. Strain EG49
N2  - 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.
KW  - Strahlenpilze
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112776
ER  - 
TY  - JOUR
A1  - Oli, Swarna
A1  - Abdelmohsen, Usama Ramadan
A1  - Hentschel, Ute
A1  - Schirmeister, Tanja
T1  - Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Fractionation
JF  - MARINE DRUGS
N2  - 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.
KW  - plakortis halichondroides
KW  - plakortide E.
KW  - protease inhibitor
KW  - slowly-binding reversible inhibitor
KW  - cathepsin
KW  - trypanosoma brucei
KW  - cysteine protease
KW  - malaria parasites
KW  - cathepsin-L
KW  - in-vitro
KW  - rhodesain
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116536
SN  - 1660-3397
VL  - 12
IS  - 5
ER  - 
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  -