We screened a myxobacterial strain collection for producers of novel chemical structures to enrich our anti-infectives hit discovery pipeline. Therefore, we fermented numerous myxobacteria in liquid media in the shake flask scale, independently, and analyzed their production profile using uHPLC-hrMS (data not shown). One strain, C. coralloides ST201330 produced a compound with a m/z [M+H] + value of 1184.56, which could not be matched to known natural products in SciFinder and DNP database searches. Thus, we purified this compound that was named Corramycin (1) from the fermentation broth of ST201330 shake flask cultures. Notably, we also identified another strain, C. coralloides MCy10984, producing the same compound. Detailed analysis of the 1D and 2D NMR spectra revealed the two-dimensional structure of Corramycin (Figure ; see SI). Corramycin exhibits a linear peptidic structure with eight α-amino acids including several unique structural features such as the so far unknown -N-methyl-β-hydroxy-histidine, a 5-amino-2,3dihydroxy-4-methoxy valeroyl moiety and an N-terminal dihydroxy butyric acid moiety. The supplementation of isotope-labelled precursor building blocks of Corramycin during the fermentation process coupled with uHPLC-hrMS analysis additionally enabled the identification of several minor Corrramycin analogues, including des-methylated (2), hydroxylated (3), doublehydroxylated (4), and hydroxylated plus glycosylated (5) Corramycins (Figure ; see SI). To assess the antibacterial activity of Corramycin, the in vitro minimal inhibitory concentrations (MICs) against several E. coli strains and some other important human pathogens were determined using a standard Clinical and Laboratory Standards Institute (CLSI) protocol. Good antibiotic activity was observed against E. coli ATCC35218 with a MIC of 1-4 µg mL -1 , but also against additional E. coli strains, including MDR ones, and S. typhimurium (4 µg mL -1 ) (Table ). ). To investigate if Corramycin exhibited a different MoA as compared to the antibiotics classes commonly used in the clinic, we assessed the MICs of Corramycin, tobramycin, Cefotaxim, Cefoxitin, Ciprofloxacin, Tetracycline, and Rifampicin against 16 clinical isolate Escherichia coli strains, which are classified carbapenem-resistant, aminoglycosideresistant, or quinolone-resistant (Supporting Table ). Notably, we could not observe cross-resistance to any of the other antibiotics. We next aimed for the identification of the corresponding BGC to gain insights into the biosynthesis and the stereochemistry of the unique structure of Corramycin. Considering the peptidic structure combined with the N-terminal dihydroxy butyric acid and the 5-amino-2,3-dihydroxy-4-methoxy valeroyl moiety, we assumed that Corramycin was produced by a hybrid NRPS-PKS. Thus, we sequenced the genomic DNA of both producer strains and screened for the BGC in the genomes, eventually identifying five streamlined core genes, comKLMNO, encoding a 12-modular hybrid NRPS-PKS assembly line (Supporting Table ). In order to identify additional genes putatively belonging to the BGC, such as genes encoding tailoring enzymes, we determined the BGC borders by comparing the genomic regions surrounding comKLMNO in both producer strains with the phylogenetically closely related non-producer strain C. coralloides DSM2259. Fifteen putative genes were identified that presumably belong to the Corramycin BGC (Supporting Figure ). Based on the in silico analysis of the putative genes involved in the Corramycin biosynthesis and feeding experiments with isotope-labelled precursors, we were able to propose a model for the biosynthesis (Figure , Supporting Table ).