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2015

Proteomic Analysis of Anti-Cancerous Scopularide Production by a Marine Microascus brevicaulis Strain and Its UV Mutant

Kramer, A., Beck, H. C., Kumar, A., Kristensen, L. P., Imhoff, J. F., & Labes, A. (2015). Proteomic Analysis of Anti-Cancerous Scopularide Production by a Marine Microascus brevicaulis Strain and Its UV Mutant. PLoS ONE, 10, e0140047. Abgerufen von http://oceanrep.geomar.de/30275/

Abstract

The marine fungus Microascus brevicaulis strain LF580 is a non-model secondary metabolite producer with high yields of the two secondary metabolites scopularides A and B, which exhibit distinct activities against tumour cell lines. A mutant strain was obtained using UV mutagenesis, showing faster growth and differences in pellet formation besides higher production levels. Here, we show the first proteome study of a marine fungus. Comparative proteomics were applied to gain deeper understanding of the regulation of production and of the physiology of the wild type strain and its mutant. For this purpose, an optimised protein extraction protocol was established. In total, 4759 proteins were identified. The central metabolic pathway of strain LF580 was mapped using the KEGG pathway analysis and GO annotation. Employing iTRAQ labelling, 318 proteins were shown to be significantly regulated in the mutant strain: 189 were down- and 129 upregulated. Proteomics are a powerful tool for the understanding of regulatory aspects: The differences on proteome level could be attributed to limited nutrient availability in the wild type strain due to a strong pellet formation. This information can be applied for optimisation on strain and process level. The linkage between nutrient limitation and pellet formation in the non-model fungus M. brevicaulis is in consensus with the knowledge on model organisms like Aspergillus niger and Penicillium chrysogenum
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2015

Journal Article

Annemarie Kramer

Hans Beck

Abhishek Kumar

Lars Kristensen

Johannes Imhoff

Antje Labes

Mutant strains

Proteomes

Protein extraction

Enzyme regulation

Fungi

Cell disruption

Protein metabolism

Biosynthesis
Prioritizing agile benefits and limitations in relation to practice usage

Solinski, A., & Petersen, K. (2015). Prioritizing agile benefits and limitations in relation to practice usage. Software Quality Journal, 1–36.
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Petersen, Kai

Abteilung/Einrichtung

FLAIR - Flensburg Artificial Intelligence Research
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2015

Journal Article

Adam Solinski

Kai Petersen
More Efficient Secure Outsourcing Methods for Bilinear Maps

Arabacı, Ö., Kiraz, M. S., Sertkaya, İ., & Uzunkol, O. (2015). More Efficient Secure Outsourcing Methods for Bilinear Maps. IACR Cryptol. ePrint Arch., 2015, 960. Abgerufen von http://eprint.iacr.org/2015/960
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Uzunkol, Osmanbey

Fachbereich

Fachbereich 3: Information und Kommunikation
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2015

Journal Article

Öznur Arabacı

Mehmet Kiraz

İsa Sertkaya

Osmanbey Uzunkol

2014

Power performance measurements of the NREL CART-2 wind turbine using a nacelle-based lidar scanner

Rettenmeier, A., Schlipf, D., Würth, I., & Cheng, P. W. (2014). Power performance measurements of the NREL CART-2 wind turbine using a nacelle-based lidar scanner. Journal of Atmospheric and Oceanic Technology, 31, 2029–2034. http://doi.org/10.1175/jtech-d-13-00154.1 (Original work published 2026)
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Schlipf, David
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2014

Journal Article

Andreas Rettenmeier

David Schlipf

Ines Würth

Po Cheng
Malettinin E, an antibacterial and antifungal tropolone produced by a marine Cladosporium strain

Silber, J., Ohlendorf, B., Labes, A., Wenzel-Storjohann, A., Näther, C., & Imhoff, J. F. (2014). Malettinin E, an antibacterial and antifungal tropolone produced by a marine Cladosporium strain. Frontiers in Marine Science, 1, 1–6. Abgerufen von http://oceanrep.geomar.de/25470/ (Original work published 2026)

Abstract

The isolation and structure elucidation of malettinins A?C (1?3) along with the new malettinin E (4) are described. The compounds were produced by the fungus Cladosporium sp. strain KF501, which was isolated from the German Wadden Sea. The malettinins are built up of tropolone/dihydropyran ring structures linked to a furan ring. The structure elucidation of the isolated compounds was achieved by means of one- and two-dimensional NMR spectroscopy supported by mass and UV data. The relative configuration of 4 was determined on the basis of single-crystal X-ray diffraction analysis. 1?4 exhibited antibacterial and antifungal activities when profiled against Xanthomonas campestris and Trichophyton rubrum. The influence of the chemical structure of the furan ring and of configurational changes on biological activities was observed.
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2014

Journal Article

Johanna Silber

Birgit Ohlendorf

Antje Labes

Arlette Wenzel-Storjohann

Christian Näther

Johannes Imhoff

marinenaturalproducts

fungalnaturalproducts

antibacterial

antifungal

Cladosporium sp.

malettinin

tropolone
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 2026)

Abstract

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 2026)

Abstract

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
Lingua Franca and its Grammar Footprint: Introducing an Index for Quantifying Grammatical Diversity in Written and Spoken Language

John, P., & Brooks, B. (2014). Lingua Franca and its Grammar Footprint: Introducing an Index for Quantifying Grammatical Diversity in Written and Spoken Language. Journal of Quantitative Linguistics, 21(1), 23. http://doi.org/https://doi.org/10.1080/09296174.2013.856130 (Original work published Dezember 2013)

Abstract

The paper introduces a method to quantify grammar diversity based on part-of-speech tagging (POS) and presents a POS diversity index which can be used for analysing written and spoken communication independently of a text’s length. For this purpose, a series of transcripts of the radio programme Lingua Franca, broadcast by the Australian Broadcast Corporation, are assessed. The radio presenter’s grammatical footprint is compared with the POS index values of the invited guests, and the hypothesis that a significant difference in the grammar structures used by the different speakers is tested for validity using a standard ANOVA calculation. Significantly different POS diversity is found in a comparison between groups of speakers. The index provides for comparative studies of grammar structures used by individual speakers or authors.
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John, Peter

Fachbereich

Fachbereich 3: Information und Kommunikation
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2014

Journal Article

Peter John

Benjamin Brooks
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)

Abstract

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)

Abstract

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

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