Mutasynthetic Production and Antimicrobial Characterization of Darobactin Analogs
Nils Böhringer, Robert C. Green, Yang Liu, Ute Mettal, Michael Marner, Seyed Majed Modaresi, Roman P. Jakob, Zerlina G. Wuisan, Timm Maier, Akira Iinishi, Sebastian Hiller, Kim Lewis, Till F. Schäberle
Abstract
Therapeutic options to combat Gram-negative bacterial pathogens are dwindling with increasing antibiotic resistance. This study presents a proof of concept for the heterologous-expression approach to expand on the novel antibiotic class of darobactins and to generate analogs with different activities and pharmacokinetic properties. In combination with the structural data of the target BamA, this approach may contribute to structure-activity relationship (SAR) data to optimize inhibitors of this essential outer membrane protein of Gram-negative pathogens.