Structure and Biosynthesis of Crocagins: Polycyclic Posttranslationally Modified Ribosomal Peptides from Chondromyces crocatus |
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Authors: | Dr. Konrad Viehrig Dr. Frank Surup Dr. Carsten Volz Dr. Jennifer Herrmann Dr. Antoine Abou Fayad Sebastian Adam Dr. Jesko Köhnke Prof. Dr. Dirk Trauner Prof. Dr. Rolf Müller |
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Affiliation: | 1. Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research and Pharmaceutical Biotechnology, Saarland University, Campus, Building E8.1, 66123 Saarbrücken, Germany;2. Helmholtz Center for Infection Research (HZI), Department Microbial Drugs, Inhoffenstraße 7, 38124 Braunschweig, Germany;3. Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstrasse 5–13, 81377 Munich, Germany |
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Abstract: | Secondary metabolome mining efforts in the myxobacterial multiproducer of natural products, Chondromyces crocatus Cm c5, resulted in the isolation and structure elucidation of crocagins, which are novel polycyclic peptides containing a tetrahydropyrrolo[2,3-b]indole core. The gene cluster was identified through an approach combining genome analysis, targeted gene inactivation in the producer, and in vitro experiments. Based on our findings, we developed a biosynthetic scheme for crocagin biosynthesis. These natural products are formed from the three C-terminal amino acids of a precursor peptide and thus belong to a novel class of ribosomally synthesized and post-translationally modified peptides (RiPPs). We demonstrate that crocagin A binds to the carbon storage regulator protein CsrA, thereby inhibiting the ability of CsrA to bind to its cognate RNA target. |
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Keywords: | biosynthesis inhibitors myxobacteria natural products RiPPs |
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