Natural antibiotics from mushrooms based on metabolic profiling

Published on November 28, 2014

How can one identify the antibiotic compounds in a complex extract without prior separation?

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The modern workflow for the functional identification and characterization of bioactive compounds for medicinal or agrochemical purposes is shown featuring a new “reverse metabolomics” method. We start with fungal fruiting bodies, a neglected source of natural products. The process chain with the collection of mushrooms, followed by their extraction, antibiotic and metabolic profiling by mass spectrometry and thereupon based property guided isolation, and eventually structure elucidation spectroscopic methods. The identification of the relevant peaks of the crude extracts thereby is aided by a “reverse metabolomics” process newly developed in our group. It uses algorithms and modern computational methods for an activity-correlation-analysis (AcorA) linking spectroscopic data from metabolic profiles of the fungal extracts to biological activity profiles of the same samples. This approach leads to a more efficient and faster recognition of novel compounds ready for further development toward their environmentally friendly application as drugs or agrochemicals.

Wessjohann Group | Leibniz Institute of Plant Biochemistry, Halle, Germany

Prof. Dr. Dr. Ludger Wessjohann is managing director of the Leibniz Institute of Plant Biochemistry and head of the Department “Bioorganic Chemistry”. He is interested in the discovery and development of new bioactive compounds, from isolation to total synthesis and medicinal chemistry optimization, thereby also using modern computational and chemoenzymatic methods.

Dr. Norbert Arnold is a mycologist and research group leader “Natural Products”.

Chelsea Harmon is a DAAD-Rise fellow from the USA.

Alexander Otto is a PhD student with expertise in antifungal assays.

Dr. Jürgen Schmidt is head of the mass spectrometry laboratory and research group leader “Spectroscopy”.

Serge Fobofou is a PhD student and DAAD fellow from Cameroon.

Nicole Hünecke is a technician in the research group “Natural Products”.

Sources

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Geissler, T.; Brandt, W., Porzel, A., Schlenzig, D., Kehlen, A., Wessjohann, L., Arnold, N.; Acetylcholinesterase inhibitors from the toadstool Cortinarius infractus, J. Bioorg. Med. Chem. 2010, 18 2173–2177, DOI: 10.1016/j.bmc.2010.01.074.

Heinke, R., Arnold, N., Wessjohann, L., Schmidt, J.; Negative ion tandem mass spectrometry of prenylated fungal metabolites and their derivatives, J. Anal. Bioanal. Chem. 2013, 405 177 – 189, DOI: 10.1007/s00216-012-6498-1.

Wessjohann, L.; Reverse metabolomics – Metabolomics in drug discovery: Connecting metabolomic profiles with phylogenetic, medicinal and flavoring properties, Metabolomics & Systems Biol., 2014, 4 (2) 70, DOI: 10.4172/2153-0769.S1.024.

Degenhardt A., Wittlake, R., Steilwind, S., Liebig, M., Runge, C., Hilmer, J.M., Krammer, G., Gohr, A. & Wessjohann, L.; Quantification of important flavour compounds in beef stocks and correlation to sensory results by “Reverse Metabolomics, In: Flavour Science (ed. by Vicente Ferreira) Amsterdam 2014 [publ. 2013], p. 15-19 ISBN 978-0-12-398549-1

Bobach, C., Schurwanz, J., Franke, K., Denkert, A., Van Sung, T., Kuster, R., Mutiso, P.C., Seeliger, B., Wessjohann, L.; Multiple readout assay for hormonal (androgenic and antiandrogenic) and cytotoxic activity of plant and fungal extracts based on differential prostate cancer cell line behavior, J. Ethnopharmacol. 2014, 155 721-730, DOI: 10.1016/j.jep.2014.06.008.

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