biostudies-literatureBohringer NHHS | National Institutes of HealthGerman Federal Ministry of Education and Research (BMBF) via a project of the Deutsche Zentrum für InfektionsforschungAntiResist: New approaches to combat antibiotic-resistant bacteriaSwiss National Science FoundationNIAID NIH HHSe0153521https://www.ebi.ac.uk/biostudies/studies/S-EPMC8694152biostudies-literatureUnknown9(3)There is great need for therapeutics against multidrug-resistant, Gram-negative bacterial pathogens. Recently, darobactin A, a novel bicyclic heptapeptide that selectively kills Gram-negative bacteria by targeting the outer membrane protein BamA, was discovered. Its efficacy was proven in animal infection models of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, thus promoting darobactin A as a promising lead compound. Originally discovered from members of the nematode-symbiotic genus <i>Photorhabdus</i>, the biosynthetic gene cluster (BGC) encoding the synthesis of darobactin A can also be found in other members of the class <i>Gammaproteobacteria</i>. Therein, the precursor peptides DarB to -F, which differ in their core sequence from darobactin A, were identified <iMicrobiology spectrumMutasynthetic Production and Antimicrobial Characterization of Darobactin Analogs.PMC869415218054151AU40_180541TTU09.818187170R01 AI158388R01AI158388Modaresi SMLewis KJakob RPIinishi AMettal UMaier TSchaberle TFHiller SLiu YGreen RMarner MWuisan ZGBohringer NfalseMutasynthetic Production and Antimicrobial Characterization of Darobactin Analogs.There is great need for therapeutics against multidrug-resistant, Gram-negative bacterial pathogens. Recently, darobactin A, a novel bicyclic heptapeptide that selectively kills Gram-negative bacteria by targeting the outer membrane protein BamA, was discovered. Its efficacy was proven in animal infection models of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, thus promoting darobactin A as a promising lead compound. Originally discovered from members of the nematode-symbiotic genus <i>Photorhabdus</i>, the biosynthetic gene cluster (BGC) encoding the synthesis of darobactin A can also be found in other members of the class <i>Gammaproteobacteria</i>. Therein, the precursor peptides DarB to -F, which differ in their core sequence from darobactin A, were identified <i2021-01-01T00:00:00Z2021 Dec2026-06-10T05:52:57.528Z2025-04-05T20:40:20.511ZS-EPMC86941523493719310.1128/spectrum.01535-21