Martin Luther University Halle-Wittenberg

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Natural products from cyanobacteria

Cyanobacteria are an under-researched source of chemically intriguing natural products    with various, often pronounced biological activities.

We currently have various projects where we work on cyanobacterial natural products.


ANoBIn - Antiinfectives from Indonesian cyanobacteria

Indonesia is a so-called biodiversity hotspot with a dense and species-rich flora and fauna. In a collaborative project (ANoBIn, Accessing Novel Bacterial Producers from Biodiversity-rich Habitats in Indonesia) with other German as well as Indonesian partners, my group strives to identify novel anti-infective metabolites biosynthesized by Indonesian cyanobacteria. The project includes sampling excursions to isolate novel cyanobacteria strains, followed by their identification and taxonomic characterization and a biological and chemical screening. Subsequent processing (cultivation, extraction, isolation and structure elucidation of active compounds) is performed for the most interesting strains. This project is funded by the German Federal Ministry of Education and Research (BMBF).

We are not only screening for natural products with direct antibacterial or anifungal activity, but are also interested in inhibitors of proteases that are currently discussed as drug targets to treat certain infections. We are e.g. searching for natural products inhibiting the protease rhodesain from Trypanosoma brucei, a pathogen causing sleeping sickness.

The project is financially supported by the BMBF and pursued by Ronja Kossack.

Cooperations:

  • Prof. Dr. Jörg Overmann; Leibniz-Institut DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen)
  • Prof. Dr. Peter Kämpfer; Institut für Angewandte Mikrobiologie, Justus-Liebig-Universität Giessen
  • Prof. Dr. Stefan Schulz; Institut für Organische Chemie, Technische Universität Braunschweig
  • Dr. Wien Kusharyoto; Laboratory for Applied Genetic Engineering and Protein Design, Indonesian Institute of Sciences (LIPI)
  • Dr. Dwi Dwi Susilaningsih Setyawan; Research Center for Biotechnology, Indonesian Institute of Sciences (LIPI)
  • Prof. Dr. Tanja Schirmeister, Institut für Pharmazie und Biochemie, Johannes Gutenberg Universität Mainz

CyanoScreen - Microcystins as drug lead compounds

Microcystins, cyclic heptapeptides from cyanobacteria, can possibly be used as lead compounds for the development of drugs    targeting certain types of cancers. Together with the company Cyano Biotech GmbH (Berlin, Germany), we are currently working on the generation of optimized structures with higher selectivity for the tumor cells, reducing their general toxicity and, thus, the side effects of these compounds. This project is funded by the German Federal Ministry for Economic Affairs and Energy (BMWi).

The microcystins have a novel mode of action for anticancer therapy (inhibition of protein phosphatases) and depend on active transport into cells in order to excert their toxicity. We try to introduce structural variations into the microcystin core structure in order to increase the selectivity towards transport into cancer cells, or to make the microcystins amenable for targeted delivery.

In this context, we also created an intreaguing tool for physiological studies  on the role of microcystins within cyanobacteria, as well as for  pharmacological studies within eukaryotic cells: We have developed unnatural microcystin congeners that can easily be chemically tagged with any kind of marker, e.g. for electron or fluorescence microscopy.

microcystin producing cyanobacteria strains

microcystin producing cyanobacteria strains

microcystin producing cyanobacteria strains

The project is financially supported by the BMWi and pursued by Julia Moschny.

Cooperations:

  • Dr. Dan Kramer, Cyano Biotech GmbH, Berlin
  • Prof. Marcus Frohme, Molekulare Biotechnologie und funktionelle Genomik, TH Wildau

Hunting down the Eagle Killer - Investigating the cause of AVM

Wheat germs contain Glycosylceramides

Wheat germs contain Glycosylceramides

AVM is a fatal neurological disease affecting freshwater fauna, mostly birds and some reptiles. One typical symptom of the disease are leasions in specific brain areas of affected birds. AVM in recent years has been observed all over the south-eastern states of the USA. The disease has been linked to cyanobacteria of the novel species Aetokthonos hydrillicola by our American collaboration partners. The cyanobacterium grows epiphytically on Hydrilla verticillata, an invasive water plant spreading aggressively throughout freshwater reservoirs in the southeast of the US. Aetokthonos' most famous victim is the national animal of the US, the bald eagle. We could isolate the cyanobacterium from AVM affected lakes and took it in culture. In this project, we aim to answer the following questions:

  • What is the chemical structure of the toxin causing AVM?
  • What is its mode of action?
  • Which environmental factors trigger the production of the neurotoxin?
  • How is the toxin biosynthesized?
  • How does the toxin travel up the food chain?

Steffen Breinlinger is working on this project.

Co-operations:

  • Prof. Susan Wilde, Warnell School of Forestry and Natural Resources, University of Georgia, Athens, USA
  • Prof. Dayton Wilde, College of Agriculture and Environmental Science, University of Georgia, Athens, USA
  • Prof. John C. Maerz, Warnell School of Forestry and Natural Resources, University of Georgia, Athens, USA
  • Prof. James Lauderdale, Department of Genetics, University of Georgia, Athens, USA

Past Projects

Antibacterial Cyclophanes from Nostoc

In collaboration with scientists at the University Greifswald, Germany  (M. Preisitsch and S. Mundt), we have been working on the structure  elucidation of cyclophanes from the cyanobacterial genus Nostoc. A screening of cyanobacteria extracts revealed an extract from a Nostoc sp.  as highly active against Gram-positive pathogens. The active compounds  were isolated and structurally characterized, resulting in 5 new and 11  known cyclophanes   . In addition to a pronounced antibacterial activity  against S. aureus and S. pneumoniae, the compounds  also displayed cytotoxicity. Presence of a carbamoyl group slightly  enhances both antibacterial and cytotoxic activity.

We have also generated derivatives of the natural products    for comparative activity testing. Furthermore, we have conducted a screening of > 100 cyanobacteria strains for novel analogs. This led to the isolation of novel compounds, the cylindrofridins   , with intreaguing structures that helped us to contribute to the elucidation of the biosynthesis of the cyclophanes.

This project has been supported by the DZIF.

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