Natural products from fungi
Nature is able to synthesize very complex structures with high biological potential, important examples are morphines, taxol, tetracyclin or avermectin. Secondary metabolites seem to be “privileged structures” – selected by evolution, synthesized by special proteins and, in the case of antibiotics, it is not surprising that these molecules have more than one target organism – they address ubiquitous targets such as the cell wall or the ribosome. It is therefore reasonable that these substances provide producers with a growth advantage in their natural habitat. Secondary metabolites produced by microorganisms are valuable for mankind. Prominent examples for fungal natural products on the market or serving as lead structures are the antibiotic penicillin, the immunosuppressant cyclosporine, the HMG-CoA reductase inhibitor lovastatin (cholesterol-lowering drug) as well as the fungizide strobilurin (lead structure for agricultural fungicide).
One of our foci is the isolation and characterization of secondary metabolites mainly produced by fungi possessing biological activities. Nevertheless, we are also interested in natural products from certain fungi to investigate their ecological function (e.g. from plant-pathogenic fungi) or from other sources (plants, bacteria).
Founded on a strain collection of approximately 20.000 fungi, extracts from small scale fermentations are evaluated for their bioactivity. Subsequently positive hits are dereplicated via fractionation. Follow-ups are realized by fermentations in large scale (20 L to 200 L), isolation of the secondary metabolites and characterization of the bioactive principle.
Screening capabilities and validation of bioactivities
To evaluate the specific bioactive potential of fungal extracts the IBWF offers multiple assay opportunities. Assays with diverse bacterial and fungal strains as well as with oomycetes, nematodes and plants are performed to detect basic activities (e.g. Enterobacter cloacae subsp. dissolvens, Escherichia coli, Eremothecium coryli, Rhizomucor miehei, Phytophthora infestans, Meloidogyne incognita, Setaria italica). In addition, germination assays with Magnaporthe oryzae, Botrytis cinarea, and Fusarium graminearum are conducted. Cytotoxicity can be tested with various cell lines (e.g. Jurkat, Hela-S3).
In addition specific assays can be performed. Either target-based assays are developed (e.g. HOG Pathway) or are transferred from cooperation partners and adjusted to our screening platform. Specific assays to investigate the mode of action (e.g. respiration) are in place to characterize secondary metabolites.
Fermentation resources and isolation tools
In order to isolate secondary metabolites in quantities needed for biological and chemical characterization several culturing methods are available at IBWF. Cultivation in small scale (various volumes for shaking or static cultures) to large scale up to 200 L (stirred cultures under process-controlled conditions) is possible. In addition, isolation processes are based on extraction (solvents, resins), fractionation (SPE, flash chromatography, centrifugal partition chromatography) and purification (preparative HPLC) are well established. These processes are supported by HPLC and HPLC/MS based techniques and IBWF’s own pure substance MS/UV-Vis-libraries for comparative analyses. Hence, fermentation processes and isolation conditions can be developed and optimized at IBWF.
Related publications
I. Buckel, L. Andernach, A. Schüffler, M. Piepenbring, T. Opatz, and E. Thines.
Scientific Reports. 2017, 7:8926. doi:10.1038/s41598-017-09157-6
C. Hong, J. Cao, C.-F. Wu, O. Kadioglu, A. Schüffler, U. Kauhl, S. M. Klauck, T. Opatz, E. Thines, N. W. Paul, and T. Efferth.
Scientific Reports. 2017, 7:11551. doi:10.1038/s41598-017-10443-6
Terphenyl Derivatives from Allantophomopsis lycopodina.
L. Andernach, L. P. Sandjo, J. C. Liermann, R. Schlämann, C. Richter, J.-P. Ferner, H. Schwalbe, A. Schüffler, E. Thines, and T. Opatz.
Journal of Natural Products. 2016, 79 (10), 2718-2725. doi:10.1021/acs.jnatprod.6b00690
Tanzawaic acids I–L: Four new polyketides from Penicillium sp. IBWF104-06.
L. P. Sandjo, E. Thines, T. Opatz, A. Schueffler.
Beilstein Journal of Organic Chemistry. 2014, 10, 251–258. doi:10.3762/bjoc.10.20
Isolactarane and sterpurane sesquiterpenoids from the basidiomycete Phlebia uda.
A. Schueffler, A., B. Wollinsky, T. Anke, J. C. Liermann, T. Opatz.
Journal of Natural Products. 2012, 75(7), 1405–1408. doi:10.1021/np3000552
Patent WO2015067800: Antifungal Penicillium strains, fungicidal extrolites thereof, and their use.
Applicant: BASF SE
Inventors: I. Siepe, T. Jabs, A. Schueffler, E. Thines, H. Anke, T. Opatz, L. P. Sandjo
Publication Date: 14.05.2015
Patent WO2014118099: Fungicidal naphthoquinones and derivatives.
Applicant: BASF SE
Inventors: C. Wiebe, J. Rheinheimer, D. Kremzow-Graw, F. Röhl, S. Schwolow, T. Opatz, A. Schueffler, H. Kunz, E. Thines
Publication Date: 07.08.2014