Publikationen

2022

Optimization of Astaxanthin Recovery in the Downstream Process of Haematococcus pluvialis

Labes, A. ., Koopmann, I. K., Möller, S. ., Elle, C. ., Hindersin, S. ., Kramer, A. ., & Labes, A. . (2022). Optimization of Astaxanthin Recovery in the Downstream Process of Haematococcus pluvialis. Foods. http://doi.org/10.3390/foods11091352
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2022

Journal Article

Antje Labes

Inga Koopmann

Simone Möller

Clemens Elle

Stefan Hindersin

Annemarie Kramer

2020

16 Biotechnology of Marine Fungi: New Workhorses and Applications

Kramer, A. ., & Labes, A. . (2020). 16 Biotechnology of Marine Fungi: New Workhorses and Applications. The Mycota III. http://doi.org/10.1007/978-3-030-49924-2_16
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2020

Journal Article

Annemarie Kramer

Antje Labes

2016

From Discovery to Production: Biotechnology of Marine Fungi for the Production of New Antibiotics

Silber, J. ., Kramer, A. ., Labes, A. ., & Tasdemir, D. . (2016). From Discovery to Production: Biotechnology of Marine Fungi for the Production of New Antibiotics. Marine Drugs, 14, 137. http://doi.org/10.3390/md14070137 (Original work published 2024)
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2016

Journal Article

Johanna Silber

Annemarie Kramer

Antje Labes

Deniz Tasdemir
Phylogenetic Relationship and Secondary Metabolite Production of Marine Fungi Producing the Cyclodepsipeptides Scopularide A and B

Kramer, A. ., Labes, A. ., & Imhoff, J. F. (2016). Phylogenetic Relationship and Secondary Metabolite Production of Marine Fungi Producing the Cyclodepsipeptides Scopularide A and B. Marine Biotechnology, 1–9. http://doi.org/10.1007/s10126-016-9707-7
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2016

Journal Article

Annemarie Kramer

Antje Labes

Johannes Imhoff

2015

Lindgomycin, an Unusual Antibiotic Polyketide from a Marine Fungus of the Lindgomycetaceae

Wu, B. ., Wiese, J. ., Labes, A. ., Kramer, A. ., Schmaljohann, R. ., & Imhoff, J. F. (2015). Lindgomycin, an Unusual Antibiotic Polyketide from a Marine Fungus of the Lindgomycetaceae. Marine Drugs, 13, 4617–4632. Abgerufen von http://oceanrep.geomar.de/29518/

Abstract

An unusual polyketide with a new carbon skeleton, lindgomycin (1), and the recently described ascosetin (2) were extracted from mycelia and culture broth of different Lindgomycetaceae strains, which were isolated from a sponge of the Kiel Fjord in the Baltic Sea (Germany) and from the Antarctic. Their structures were established by spectroscopic means. In the new polyketide, two distinct domains, a bicyclic hydrocarbon and a tetramic acid, are connected by a bridging carbonyl. The tetramic acid substructure of compound 1 was proved to possess a unique 5-benzylpyrrolidine-2,4-dione unit. The combination of 5-benzylpyrrolidine-2,4-dione of compound 1 in its tetramic acid half and 3-methylbut-3-enoic acid pendant in its decalin half allow the assignment of a new carbon skeleton. The new compound 1 and ascosetin showed antibiotic activities with IC50 value of 5.1 ($\pm$0.2) ?M and 3.2 ($\pm$0.4) \ensuremath\muM, respectively, against methicillin-resistant Staphylococcus aureus.
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2015

Journal Article

Bin Wu

Jutta Wiese

Antje Labes

Annemarie Kramer

Rolf Schmaljohann

Johannes Imhoff

MRSA

antibiotic

lindgomycin

marine fungi

marine natural products
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

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

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
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
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

2013

Higher yields of cyclodepsipetides from Scopulariopsis brevicaulis by random mutagenesis

Paun, L. ., Kramer, A. ., Hihlal, E. ., Labes, A. ., Imhoff, J. F., & Kempken, F. . (2013). Higher yields of cyclodepsipetides from Scopulariopsis brevicaulis by random mutagenesis. In 27. Fungal Genetics Conference. Abgerufen von http://oceanrep.geomar.de/22016/

Abstract

The ascomycete Scopulariopsis brevicaulis, which was isolated from the marine sponge Tethya aurantium, produces two cyclodepsipeptides, scopularides A and B [1]. Both peptides exhibit activity against several tumor cell lines. Within the EU-project MARINE FUNGI (EU FP7, 265926) one of our aims is to enhance the production of these secondary metabolites. We are in the process to establish two ways of random mutagenesis by both UV radiation and transposon-mediated. To this end we created UV-mutants and a miniaturised screening method was developed. UV-radiation was performed at 312 nm and the survival rate was set to 1 \%. With this method a mutant library was established. To screen these mutants for higher secondary metabolites production, we developed a miniaturised screening method which includes decreased cultivation volume, fast extraction and an optimised LC-MS analysis format. Using the UV mutagenesis, we were able to identify several mutants with a higher scopularide production in comparison to the wild type. One of these mutants, which produces three times more biomass and more than double the amount of scopularide A, has been used for another round of mutation. Next generation sequencing is being employed to identify the molecular genetic basis of the observed mutations. In parallel we employ transposable elements to introduce mutants [2]. The impact of transposons on gene expression as well as their ability to cause major mutations within the genome or single genes makes them an interesting tool for random mutagenesis [3, 4, 5]. We employ the Vader transposon in its homologous host and found that Vader mostly integrates within or very close to genes. Thus it appears to be a useful tool for transposon-mediated mutagenesis in A. niger (6). At current we try to enhance its usability by modifying the Vader element.
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2013

Conference Paper

Linda Paun

Annemarie Kramer

ElKbir Hihlal

Antje Labes

Johannes Imhoff

Frank Kempken

2022

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2015

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2014

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