Innovative microbial resources for new anti-infectives
In spite of major technological advances in chemical synthesis, natural products from microorganisms continue to be the major source for novel chemical anti-infective scaffolds exhibiting new modes of action. Innovative cultivation techniques provide immense opportunities for finding novel antibiotic classes produced by microbes previously considered “non-culturable”. Therefore, this project aims at improving the earliest stage of antibiotic discovery to ensure a constant re-supply of the drug development pipeline with novel antibiotic hits.
In a concerted action, four DZIF partner sites (HZI/HIPS, University of Bonn, University of Tübingen, HKI Jena) renowned for natural compound research will develop and apply new cultivation, production and screening technologies for the identification of novel producers and the isolation of new antibiotic compounds. Each partner site pursues, in a complementary setup, different techniques and focuses on different groups of microorganisms.
Our group is specialized in isolation, cultivation and microbiological description of novel strains, genera and families of myxobacteria, which already have delivered a wide array of novel antibiotic compounds in the past (Ref. 1-4). Promising new substances with relevant bioactivity and broad spectrum efficacy will be the basis for subsequent lead structure development und optimization during later pre-clinical and clinical phases.
- Held J, Gebru T, Kalesse M, Jansen R, Gerth K, Müller R & Mordmüller B (2014) Antimalarial activity of the myxobacterial macrolide chlorotonil A. Antimicrob. Agents Chemother. 58: 6378–6384
- Baumann S, Herrmann J, Raju R, Steinmetz H, Mohr KI, Hüttel S, Harmrolfs K, Stadler M & Müller R (2014) Cystobactamids: myxobacterial topoisomerase inhibitors exhibiting potent antibacterial activity. Angew. Chem. Int. Ed. Engl. 53: 14605–14609.
- Wenzel SC, Hoffmann H, Zhang J, Debussche L, Haag-Richter S, Kurz M, Nardi F, Lukat P, Kochems I, Tietgen H, Schummer D, Nicolas J-P, Calvet L, Czepczor V, Vrignaud P, Mühlenweg A, Pelzer S, Müller R & Brönstrup M (2015) Production of the bengamide class of marine natural products in myxobacteria: biosynthesis and structure-activity relationships. Angew. Chem. Int. Ed. Engl. 54: 15560–15564.
- Hüttel S, Testolin G, Herrmann J, Planke T, Gille F, Moreno M, Stadler M, Brönstrup M, Kirschning A & Müller R (2017) Discovery and total synthesis of natural cystobactamid derivatives with superior activity against Gram-negative pathogens. Angew. Chem. Int. Ed. Engl., DOI: 10.1002/anie.201705913.
- Microbial Natural Products- Prof. Dr. Rolf Müller
DZIF - German Centre for Infection Research