Microbial Natural Products
Our Research
Myxobacteria are capable of producing a plenitude of natural products with high structural and functional diversity. Accordingly, we find myxobacterial substances acting against all kinds of organisms, ranging from bacteria and fungi to mammalian cells or even viruses. We apply activity- and structure-guided approaches to identify bioactive compounds, but also use modern genome mining tools to shed light on the hidden biosynthetic potential of underexplored myxobacteria. Following their identification, we structurally characterize novel compounds and solve the molecular mechanisms underlying their biosynthesis and mode of action. This provides vital information for the biotechnological and chemical improvement of these substances. Our goal is to generate and develop hit and lead compounds, which are eventually transferred to the clinic. We have successfully established an in-house strain collection containing more than 10.000 unique myxobacterial strains, isolated from places all over the world. This collection is continuously expanded and represents the basis of our pursuit for exciting novel chemistry.
Our Research
Myxobacteria are capable of producing a plenitude of natural products with high structural and functional diversity. Accordingly, we find myxobacterial substances acting against all kinds of organisms, ranging from bacteria and fungi to mammalian cells or even viruses. We apply activity- and structure-guided approaches to identify bioactive compounds, but also use modern genome mining tools to shed light on the hidden biosynthetic potential of underexplored myxobacteria. Following their identification, we structurally characterize novel compounds and solve the molecular mechanisms underlying their biosynthesis and mode of action. This provides vital information for the biotechnological and chemical improvement of these substances. Our goal is to generate and develop hit and lead compounds, which are eventually transferred to the clinic. We have successfully established an in-house strain collection containing more than 10.000 unique myxobacterial strains, isolated from places all over the world. This collection is continuously expanded and represents the basis of our pursuit for exciting novel chemistry.
Prof Dr Rolf Müller
We mainly focus on the discovery of microbial natural products in order to develop new antibiotics to combat infectious diseases.
Rolf Müller studied pharmacy at Bonn University and obtained his PhD at the Department of Pharmaceutical Biology. In 1996, he went to the Department of Chemistry at the University of Washington in Seattle, USA . This was when he began to investigate the production of antibiotics in bacteria. Two years later he returned to Germany as a junior group leader at the German Research Centre for Biotechnology (GBF, now the HZI) in Braunschweig. In 2000, he completed his habilitation thesis at the Technische Universität Braunschweig on the biosynthesis of antibiotics in actinomycetes and myxobacteria.
Since October 2003, Rolf Müller has held a chair as professor of Pharmaceutical Biotechnology at Saarland University. In 2009 Rolf Müller became the managing director of the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), heads the Department of “Microbial Natural Products” and co-founded the PharmBioTec GmbH in Saarbrücken. Within the German Center for Infection Research (DZIF) Rolf Müller coordinates the thematic unit “Novel Antibiotics.”
His research has already earned the Phoenix-Pharmacy Research Award three times (2001,2007,2016) the DECHEMA Award for the Natural Products Research (2002), the BioFuture Award of the GermanFederal Ministry for Education and Research (2003), and the DECHEMA Award of the Max-Buchner Research Foundation (2010).
Since 2012 he has been a member of the German National Academy of Science and Engineering. In 2016 he also became elected member of National Academy of Sciences (Leopoldina). Additionally, he has been awarded the Gottfried Wilhelm Leibniz Prize 2021, the Charles Thom Award 2023, the Tu Youyou Award 2024, as well as the Carl-Mannich-Medal 2025.
Selected Publications
Xie, F., Zhao, H., Liu, J., Yang, X., Neuber, M., Agrawal, A.A., Kaur, A., Herrmann, J., Kalinina, O.V., Wie, X., Müller, R.,* Fu, C.* (2024) Autologous DNA mobilization and multiplication expedite natural products discovery from bacteria. Science, 386 ,eabq7333. DOI:10.1126/science.abq7333
Fu, C., Liu, Y., Walt, C., Rasheed, S., Bader, C., Lukat, P., Neuber, M., Haeckl, F., Blankenfeldt, W., Kalinina, O., and Müller, R.* (2024) Elucidation of unusual biosynthesis and DnaN-targeting mode of action of potent anti-tuberculosis antibiotics Mycoplanecins. Nat. Commun. 15, 791. DOI: 10.1038/s41467-024-44953-5
Garcia, R., Popoff, A., Bader, C.D., Löhr, J., Walesch, S., Walt, C., Boldt, J., Bunk, B., Haeckl, F.P.J., Gunesch, A.P., Birkelbach, J., Nübel, U., Pietschmann, T., Bach, T., and Müller, R.* (2024) Discovery of the Pendulisporaceae: An extremotolerant myxobacterial family with distinct sporulation behavior and prolific specialized metabolism. Chem. DOI: 10.1016/j.chempr.2024.04.019
Hofer, W., Deschner, F., Jézéquel, G., Pessanha de Carvalho, L., Abdel-Wadood, N., Pätzold, L., Bernecker, S., Morgenstern, B., Kany, A.M., Große, M., Stadler, M., Bischoff, M., Hirsch, A.K.H., Held, J., Herrmann, J.,* and Müller, R.* (2024) Functionalization of Chlorotonils: Dehalogenil as promising lead compound for in vivo application. Angew. Chem. Int. Ed., 63, e202319765. DOI: 10.1002/anie.202319765
Kling, A., Lukat, P., Almeida, D.V., Bauer, A., Fontaine, E, Sordello, S., Zaburannyi, N., Herrmann, J., Wenzel, S.C., König, C., Ammerman, N.C., Barrio, M.B., Borchers, K., Bordon-Pallier, F., Brönstrup, M., Courtemanche, G., Gerlitz, M., Geslin, M., Hammann, P., Heinz, D.W., Hoffmann, H., Klieber, S., Kohlmann, M., Kurz, M., Lair, C., Matter, H., Nuermberger, E., Sandeep T., Fraisse, L., Grosset, J.H., Lagrange, S. and Müller, R.* (2015) Targeting DnaN for tuberculosis therapy using novel griselimycins, Science, 348 (6239): 1106-12. DOI: 10.1126/science.aaa4690
A complete list of publications can be found on the HIPS website.
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