Herein, we report the discovery of the novel natural product Corramycin which we isolated from the myxobacterium C. coralloides. Structure elucidation via NMR revealed unprecedented structural features as, for example, the (2R,3S)--N-methyl-β-hydroxy-histidine moiety. Corramycin showed antibacterial activity in the low µM range against E. coli, including carbapenem-, aminoglycoside-and quinolone-resistant clinical isolate strains and no cytotoxicity against mammalian cell lines. Furthermore, after identification and in silico analysis of the BGC, we propose a biosynthesis model by a hybrid NRPS-PKS assembly line, including the probable presence of a pre-drug mechanism, and predicted the stereochemistry of 8 out of 13 stereocenters based on the functional subtype of the respective C domains. We also describe the total synthesis of Corramycin, which enabled the elucidation of the absolute stereo configuration, thereby verifying the prediction of the stereocenters. The total synthesis also allowed bypassing the low yields obtained by fermentation. Intravenous administration of Corramycin in mice infected with E. coli resulted in 60 % survival of all test animals after four days when administering at 30 mg kg -1 on the first day, importantly, without toxic side effects observed. Finally, we provide evidence that Corramycin showed a much lower frequency of resistance (FoR) using minimal rather than rich media which is suggested to be due to the uptake of Corramycin by two transporter systems in E. coli, SbmA and YejABEF.