Structure Elucidation, Total Synthesis, Antibacterial In Vivo Efficacy and Biosynthesis Proposal of Myxobacterial Corramycin**

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.