Structure Elucidation, Total Synthesis, Antibacterial In Vivo Efficacy and Biosynthesis Proposal of Myxobacterial Corramycin**
Cédric Couturier, Sebastian Groß, Alexander von Tesmar, Judith Hoffmann, Selina Deckarm, Anouchka Fievet, Nelly Dubarry, Thomas Taillier, Christoph Pöverlein, Heike Stump, Michael Kurz, Luigi Toti, Sabine Haag Richter, Dietmar Schummer, Philippe Sizun, Michael Hoffmann, Ram Prasad Awal, Nestor Zaburannyi, Kirsten Harmrolfs, Joachim Wink, Emilie Lessoud, Thierry Vermat, Veronique Cazals, Sandra Silve, Armin Bauer, Michaël Mourez, Laurent Fraisse, Corinne Leroi‐Geissler, Astrid Rey, Stéphanie Versluys, Eric Bacqué, Rolf Müller, Stéphane Renard
Abstract
Abstract Herein, we describe the myxobacterial natural product Corramycin isolated from Corallococcus coralloides . The linear peptide structure contains an unprecedented (2 R ,3 S )‐γ‐ N ‐methyl‐β‐hydroxy‐histidine moiety. Corramycin exhibits anti‐Gram‐negative activity against Escherichia coli ( E. coli ) and is taken up via two transporter systems, SbmA and YejABEF. Furthermore, the Corramycin biosynthetic gene cluster (BGC) was identified and a biosynthesis model was proposed involving a 12‐modular non‐ribosomal peptide synthetase/polyketide synthase. Bioinformatic analysis of the BGC combined with the development of a total synthesis route allowed for the elucidation of the molecule's absolute configuration. Importantly, intravenous administration of 20 mg kg −1 of Corramycin in an E. coli mouse infection model resulted in 100 % survival of animals without toxic side effects. Corramycin is thus a promising starting point to develop a potent antibacterial drug against hospital‐acquired infections.