@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{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{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} } @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{UteReisbergHildebrandtetal.2013, author = {Ute, Hentschel and Reisberg, Eva E. and Hildebrandt, Ulrich and Riederer, Markus}, title = {Distinct Phyllosphere Bacterial Communities on Arabidopsis Wax Mutant Leaves}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0078613}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96699}, year = {2013}, abstract = {The phyllosphere of plants is inhabited by diverse microorganisms, however, the factors shaping their community composition are not fully elucidated. The plant cuticle represents the initial contact surface between microorganisms and the plant. We thus aimed to investigate whether mutations in the cuticular wax biosynthesis would affect the diversity of the phyllosphere microbiota. A set of four Arabidopsis thaliana eceriferum mutants (cer1, cer6, cer9, cer16) and their respective wild type (Landsberg erecta) were subjected to an outdoor growth period and analysed towards this purpose. The chemical distinctness of the mutant wax phenotypes was confirmed by gas chromatographic measurements. Next generation amplicon pyrosequencing of the bacterial communities showed distinct community patterns. This observation was supported by denaturing gradient gel electrophoresis experiments. Microbial community analyses revealed bacterial phylotypes that were ubiquitously present on all plant lines (termed "core" community) while others were positively or negatively affected by the wax mutant phenotype (termed "plant line-specific" community). We conclude from this study that plant cuticular wax composition can affect the community composition of phyllosphere bacteria.}, language = {en} } @article{AbdelmohsenSzesnyOthmanetal.2012, author = {Abdelmohsen, Usama Ramadan and Szesny, Matthias and Othman, Eman Maher and Schirmeister, Tanja and Grond, Stepanie and Stopper, Helga and Hentschel, Ute}, title = {Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76279}, year = {2012}, abstract = {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.}, subject = {Biologie}, language = {en} } @article{PimentelElardoGrozdanovProkschetal.2012, author = {Pimentel-Elardo, Sheila Marie and Grozdanov, Lubomir and Proksch, Sebastian and Hentschel, Ute}, title = {Diversity of Nonribosomal Peptide Synthetase Genes in the Microbial Metagenomes of Marine Sponges}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75990}, year = {2012}, abstract = {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.}, subject = {Biologie}, language = {en} } @article{VillalobosWieseImhoffetal.2019, author = {Villalobos, Alvaro S. and Wiese, Jutta and Imhoff, Johannes F. and Dorador, Cristina and Keller, Alexander and Hentschel, Ute}, title = {Systematic affiliation and genome analysis of Subtercola vilae DB165T with particular emphasis on cold adaptation of an isolate from a high-altitude cold volcano lake}, series = {Microorganisms}, volume = {7}, journal = {Microorganisms}, number = {4}, issn = {2076-2607}, doi = {10.3390/microorganisms7040107}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197394}, year = {2019}, abstract = {Among the Microbacteriaceae the species of Subtercola and Agreia form closely associated clusters. Phylogenetic analysis demonstrated three major phylogenetic branches of these species. One of these branches contains the two psychrophilic species Subtercola frigoramans and Subtercola vilae, together with a larger number of isolates from various cold environments. Genomic evidence supports the separation of Agreia and Subtercola species. In order to gain insight into the ability of S. vilae to adapt to life in this extreme environment, we analyzed the genome with a particular focus on properties related to possible adaptation to a cold environment. General properties of the genome are presented, including carbon and energy metabolism, as well as secondary metabolite production. The repertoire of genes in the genome of S. vilae DB165\(^T\) linked to adaptations to the harsh conditions found in Llullaillaco Volcano Lake includes several mechanisms to transcribe proteins under low temperatures, such as a high number of tRNAs and cold shock proteins. In addition, S. vilae DB165\(^T\) is capable of producing a number of proteins to cope with oxidative stress, which is of particular relevance at low temperature environments, in which reactive oxygen species are more abundant. Most important, it obtains capacities to produce cryo-protectants, and to combat against ice crystal formation, it produces ice-binding proteins. Two new ice-binding proteins were identified which are unique to S. vilae DB165\(^T\). These results indicate that S. vilae has the capacity to employ different mechanisms to live under the extreme and cold conditions prevalent in Llullaillaco Volcano Lake.}, language = {en} } @article{ChengOthmanStopperetal.2017, author = {Cheng, Cheng and Othman, Eman M. and Stopper, Helga and Edrada-Ebel, RuAngelie and Hentschel, Ute and Abdelmohsen, Usama Ramadan}, title = {Isolation of petrocidin A, a new cytotoxic cyclic dipeptide from the marine sponge-derived bacterium \(Streptomyces\) sp. SBT348}, series = {Marine Drugs}, volume = {15}, journal = {Marine Drugs}, number = {12}, doi = {10.3390/md15120383}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172644}, year = {2017}, abstract = {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.}, language = {en} }