Structure and Biosynthesis of Crocagins: Polycyclic Posttranslationally Modified Ribosomal Peptides from Chondromyces crocatus. Issue 26 (23rd May 2017)

• Record Type: Journal Article
• Authors: Viehrig, Konrad; Surup, Frank; Volz, Carsten; Herrmann, Jennifer; Abou Fayad, Antoine; Adam, Sebastian; Köhnke, Jesko; Trauner, Dirk; Müller, Rolf
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 26(2017)
• Page Start: 7407
• Page End: 7410
• Publication Date: 2017-05-23
• Subjects: biosynthesis -- inhibitors -- myxobacteria -- natural products -- RiPPs; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201612640
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : Ribosomally synthesized and posttranslationally 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.