Publikationen

2014

• Mit der Kraft des Meeres gegen Krebs

  Lange, B. ., & Labes, A. . (2014). Mit der Kraft des Meeres gegen Krebs. Meer Und Küste, 5. Abgerufen von http://oceanrep.geomar.de/25497/ (Original work published 2024)

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  Für die Behandlung schwerer Erkrankungen wie Krebs und entzündlicher Leiden gibt es dringenden Bedarf an neuen Substanzen für effizientere und schonenderer Therapien mit weniger Nebenwirkungen

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  • 2014
  • Journal Article
  • • Beate Lange
    • Antje Labes

• A Phenotypic Screening Approach to Identify Anticancer Compounds Derived from Marine Fungi

  Ellinger, B. ., Silber, J. ., Prashar, A. ., Landskron, J. ., Weber, J. ., Rehermann, S. ., … Imhoff, J. F. (2014). A Phenotypic Screening Approach to Identify Anticancer Compounds Derived from Marine Fungi. ASSAY and Drug Development Technologies, 12, 162–175. Abgerufen von http://oceanrep.geomar.de/24658/ (Original work published 2024)

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  This study covers the isolation, testing, and identification of natural products with anticancer properties. Secondary metabolites were isolated from fungal strains originating from a variety of marine habitats. Strain culture protocols were optimized with respect to growth media composition and fermentation conditions. From these producers, isolated compounds were screened for their effect on the viability and proliferation of a subset of the NCI60 panel of cancer cell lines. Active compounds of interest were identified and selected for detailed assessments and structural elucidation using nuclear magnetic resonance. This revealed the majority of fungal-derived compounds represented known anticancer chemotypes, confirming the integrity of the process and the ability to identify suitable compounds. Examination of effects of selected compounds on cancer-associated cell signaling pathways used phospho flow cytometry in combination with 3D fluorescent cell barcoding. In parallel, the study addressed the logistical aspects of maintaining multiple cancer cell lines in culture simultaneously. A potential solution involving microbead-based cell culture was investigated (BioLevitator, Hamilton). Selected cell lines were cultured in microbead and 2D methods and cell viability tests showed comparable compound inhibition in both methods (R-2=0.95). In a further technology assessment, an image-based assay system was investigated for its utility as a possible complement to ATP-based detection for quantifying cell growth and viability in a label-free manner.

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  • 2014
  • Journal Article
  • • Bernhard Ellinger
    • Johanna Silber
    • Anjali Prashar
    • Johannes Landskron
    • Jonas Weber
    • Sarah Rehermann
    • Franz-Josef Müller
    • Stephen Smith
    • Stephen Wrigley
    • Kjetil en
    • Philip Gribbon
    • Antje Labes
    • Johannes Imhoff
  • • marine fungi
    • natural products
    • cancer
    • pharmacology
    • leukemia

• Development and Validation of a Fast and Optimized Screening Method for Enhanced Production of Secondary Metabolites Using the Marine Scopulariopsis brevicaulis Strain LF580 Producing Anti-Cancer Active Scopularide A and B

  Kramer, A. ., Paun, L. ., Imhoff, J. F., Kempken, F. ., & Labes, A. . (2014). Development and Validation of a Fast and Optimized Screening Method for Enhanced Production of Secondary Metabolites Using the Marine Scopulariopsis brevicaulis Strain LF580 Producing Anti-Cancer Active Scopularide A and B. PLoS ONE, 9, e103320. Abgerufen von http://oceanrep.geomar.de/25471/ (Original work published Juli 2014)

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  Natural compounds from marine fungi are an excellent source for the discovery and development of new drug leads. The distinct activity profiles of the two cyclodepsipeptides scopularide A and B against cancer cell lines set their marine producer strain Scopulariopsis brevicaulis LF580 into the focus of the EU project MARINE FUNGI. One of the main goals was the development of a sustainable biotechnological production process for these compounds. The secondary metabolite production of strain LF580 was optimized by random mutagenesis employing UV radiation. For a fast and reliable detection of the intracellular secondary metabolite production level, a miniaturized bioactivity-independent screening method was developed, as the random mutagenesis yielded a large number of mutants to be analysed quantitatively and none of the existing hyphenated bioassay-dependent screening systems could be applied. The method includes decreased cultivation volume, a fast extraction procedure as well as an optimized LC-MS analysis. We show that deviation could be specifically reduced at each step of the process: The measuring deviation during the analysis could be minimized to 5\% and technical deviation occurring in the downstream part to 10?15\%. Biological variation during the cultivation process still has the major influence on the overall variation. However, the approach led to a 10-fold reduction of time and similar effects on costs and effort compared to standard reference screening methods. The method was applied to screen the UV-mutants library of Scopulariopsis brevicaulis LF580. For validation purposes, the occurring variations in the miniaturized scale were compared to those in the classical Erlenmeyer flask scale. This proof of concept was performed using the wild type strain and 23 randomly selected mutant strains. One specific mutant strain with an enhanced production behavior could be obtained.

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  • 2014
  • Journal Article
  • • Annemarie Kramer
    • Linda Paun
    • Johannes Imhoff
    • Frank Kempken
    • Antje Labes
  • • Drug metabolism
    • Fungi
    • Library screening
    • Linear regression analysis
    • Liquid chromatography-mass spectrometry
    • Mutant strains Secondary metabolism
    • Ultraviolet radiation

• Nature?s Lab for Derivatization: New and Revised Structures of a Variety of Streptophenazines Produced by a Sponge-Derived Streptomyces Strain

  Kunz, A. L., Labes, A. ., Wiese, J. ., Bruhn, T. ., Bringmann, G. ., & Imhoff, J. F. (2014). Nature?s Lab for Derivatization: New and Revised Structures of a Variety of Streptophenazines Produced by a Sponge-Derived Streptomyces Strain. Marine Drugs, 12, 1699–1714. Abgerufen von http://oceanrep.geomar.de/24372/ (Original work published März 2014)

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  Eight streptophenazines (A?H) have been identified so far as products of Streptomyces strain HB202, which was isolated from the sponge Halichondria panicea from the Baltic Sea. The variation of bioactivities based on small structural changes initiated further studies on new derivatives. Three new streptophenazines (I?K) were identified after fermentation in the present study. In addition, revised molecular structures of streptophenazines C, D, F and H are proposed. Streptophenazines G and K exhibited moderate antibacterial activity against the facultative pathogenic bacterium Staphylococcus epidermidis and against Bacillus subtilis. All tested compounds (streptophenazines G, I?K) also showed moderate activities against PDE 4B.

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  • 2014
  • Journal Article
  • • Anna Kunz
    • Antje Labes
    • Jutta Wiese
    • Torsten Bruhn
    • Gerhard Bringmann
    • Johannes Imhoff
  • • marine natural product
    • phenazine
    • Baltic Sea
    • Streptomyces
    • Halichondria panicea
    • HPLC-DAD/MS
    • fermentation
    • PDE 4
    • antibiotic

• Bioactive metabolites of a marine Calcarisporium sp.

  Silber, J. ., Ohlendorf, B. ., Erhard, A. ., Labes, A. ., & Imhoff, J. F. (2014). Bioactive metabolites of a marine Calcarisporium sp. In ELRIG 2014 Research and Innovation - Impact into Cancer. Abgerufen von http://oceanrep.geomar.de/25551/

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  • 2014
  • Conference Paper
  • • Johanna Silber
    • Birgit Ohlendorf
    • Arlette Erhard
    • Antje Labes
    • Johannes Imhoff

• Presentations of the scientific briefing "New frontiers in Blue Biotechnology - Research and SME Alliances in Early Drug Discovery"

  Labes, A. ., & Imhoff, J. F. (2014). Presentations of the scientific briefing "New frontiers in Blue Biotechnology - Research and SME Alliances in Early Drug Discovery". In European Parliament. Abgerufen von http://oceanrep.geomar.de/26366/

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  • 2014
  • Conference Paper
  • • Antje Labes
    • Johannes Imhoff

• Proteomic analysis of Scopulariopsis brevicaulis LF580 and its mutant strain M26 for the production of the cyclodepsipeptides scopularide A and B

  Kramer, A. ., Beck, H. C., Kumar, A. ., Labes, A. ., & Imhoff, J. F. (2014). Proteomic analysis of Scopulariopsis brevicaulis LF580 and its mutant strain M26 for the production of the cyclodepsipeptides scopularide A and B. In 4. Gemeinsame Jahrestagung der Deutschen Gesellschaft für Hygiene und Mikrobiologie (DGHM) e. V. zusammen mit der Vereinigung für Allgemeine und Angewandte Mikrobiologie (VAAM) e. V. Abgerufen von http://oceanrep.geomar.de/26372/

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  • 2014
  • Conference Paper
  • • Annemarie Kramer
    • H. Beck
    • Abhishek Kumar
    • Antje Labes
    • Johannes Imhoff

• Establishing the Secondary Metabolite Profile of a Marine Fungus: Tolypocladium geodes MF458

  Kebede, B. ., Wrigley, S. ., Prashar, A. ., Rahlff, J. ., Ellinger, B. ., Silber, J. ., & Labes, A. . (2014). Establishing the Secondary Metabolite Profile of a Marine Fungus: Tolypocladium geodes MF458. In ELRIG 2014 Research and Innovation - Impact into Cancer. Abgerufen von http://oceanrep.geomar.de/25552/

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  • 2014
  • Conference Paper
  • • Bethlehem Kebede
    • Stephen Wrigley
    • Anjali Prashar
    • Janina Rahlff
    • Bernhard Ellinger
    • Johanna Silber
    • Antje Labes

• Production of scopularide A in submerged culture with Scopulariopsis brevicaulis

  Tamminen, A. ., Kramer, A. ., Labes, A. ., & Wiebe, M. G. (2014). Production of scopularide A in submerged culture with Scopulariopsis brevicaulis. Microbial Cell Factories, 13, 1–7. http://doi.org/10.1186/1475-2859-13-89

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  • 2014
  • Journal Article
  • • Anu Tamminen
    • Annemarie Kramer
    • Antje Labes
    • Marilyn Wiebe

• A complete view on the aquatic-derived fungal phylogeny and ecology

  Yilmaz, P. ., Glöckner, F. O., Imhoff, J. F., Labes, A. ., Panzer, K. ., Schmaljohann, R. ., … Reich, M. . (2014). A complete view on the aquatic-derived fungal phylogeny and ecology. In 15. International Symposium on Microbiology Ecology. Abgerufen von http://oceanrep.geomar.de/26376/

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  • 2014
  • Conference Paper
  • • P. Yilmaz
    • F. Glöckner
    • Johannes Imhoff
    • Antje Labes
    • K. Panzer
    • Rolf Schmaljohann
    • M. Weiß
    • Jutta Wiese
    • M. Reich