Structure and Biosynthesis of Crocagins: Polycyclic Postranslationally Modified Ribosomal Peptides from Chondromyces crocatus

Angewandte Chemie - International Edition

4 years ago

Structure and Biosynthesis of Crocagins: Polycyclic Postranslationally Modified Ribosomal Peptides from Chondromyces crocatus

Jennifer Herrmann, Sebastian Adam, Antoine Abou Fayad, Konrad Viehrig, Carsten Volz, Dirk Trauner, Frank Surup, Rolf Müller, Jesko Köhnke

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. Ribosomally synthesized and post-translationally modified peptides (RiPPs) were isolated from a myxobacterial producer. The unusual tetracyclic peptide scaffold of these crocagins turned out to originate from a ribosomally assembled precursor peptide. Isolation, structure elucidation, mutagenesis of the producer, and in vitro experiments are presented.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201612640