Interfakultäres Institut für Mikrobiologie und Infektionsmedizin

Secondary Metabolites

Prof. Dr. Timo Niedermeyer

The Niedermeyer group has moved to the University of Halle-Wittenberg.

You will find our new web appearance under the following link

Search for novel antiinfective and cytotoxic lead compounds

The Niedermeyer group is part of the German Center for Infection research (DZIF). Our responsibility within the DZIF is to find natural products that have e.g. antibacterial, antifungal or antiviral activity and that can potentially be developed into drug substances used to treat infectious diseases.

Why natural products?

Natural products, or secondary metabolites, have an impressive track record in lead and drug discovery in general and especially in antiinfectives discovery. More than half of all approved antiinfective drugs are derived from or inspired by natural products. Some of the most prominent examples for natural products or their analogs in antiinfective therapies are e.g. the penicillins, erythromycin, or tetracyclins.

Our focus

We focus on microorganisms as the source for novel secondary metabolites. One of the microorganism groups of interest are the actinomycetes, well known and prolific bacterial producers of antiinfective compounds. Another bacteria group we work on are cyanobacteria, which are much less well studied. Last but not least, we are also interested in natural products from basidiomycetes and plants.

Our approach

First, we usually conduct a chemical and bioactivity screening of novel bacterial isolates. For the chemical screening, we use analytical techniques such as high-performance liquid chromatography coupled with diode array detectors and mass spectrometers (HPLC-DAD-MS). Using this technique, and supported by our in-house natural product database, we identify microorganism strains that produce novel chemistry. For the primary bioactivity testing, a set of agar diffusion assays and microplate based assays are used to detect antimicrobial activities. Promising microorganism strains that give hits in either of these screens are then cultivated on a larger scale (e.g. 10, 20 or 100 L culture volume), and extracts are generated from the biomass or the cultivation medium using various techniques such as solvent extraction or polystyrene resin adsorption. These extracts are fractionated using various preparative chromatographic techniques depending on the physico-chemical properties of the compounds of interest. The fractionation steps are monitored by analytical HPLC as well as bioactivity assays, until we have a pure active compound in our hands. Following structure elucidation by techniques such as nuclear magnetic resonance spectroscopy (NMR) and high-resolution tandem mass spectrometry (HRMSn), the compounds bioactivities are characterized in more detail.

Our compound collection

The Institute for Microbiology at the Eberhard Karls University Tübingen has a very rich history in actinomycete natural product research. Decades of research on the isolation and characterization of secondary metabolites in the groups of Prof. H. Zähner and H.-P. Fiedler have generated a decent library of secondary metabolites that we have arranged into a ready-to-screen compound library, which is available for collaboration partners. If you are interested in more details concerning this library, please visit the website dedicated to our compound collection (coming soon).

Current research interests

Our main research interest is the isolation and structure elucidation of bioactive, especially antiinfective secondary metabolites using innovative chromatography techniques, NMR, MS and computer assisted structure elucidation (CASE) techniques. We are also interested in the use of instrumental analytics (especially MS) in fermentation monitoring and bioactivity assays, and in the analysis and characterization of the chemical interaction of (micro-)organisms.

For more information on current projects, please visit the Projects website.