Improved broad-spectrum antibiotics against Gram-negative pathogens <i>via</i> darobactin biosynthetic pathway engineering
Sebastian Groß, Fabian Panter, Domen Pogorevc, Carsten E. Seyfert, Selina Deckarm, Chantal D. Bader, Jennifer Herrmann, Rolf Müller
Abstract
-adenosyl-l-methionine-dependent enzyme, are required for darobactin formation. Co-expression of two additional genes associated with the BGCs in hypothetical producer strains identified a proteolytic detoxification mechanism as a potential self-resistance strategy in native producers. Taken together, we describe a versatile heterologous darobactin platform allowing the production of unprecedented active derivatives in good yields, and we provide first experimental evidence for darobactin biosynthesis processes.
Topics & Concepts
AntibioticsBroad spectrumGramMicrobiologyGram-negative bacteriaBiologyComputational biologyChemistryBacteriaCombinatorial chemistryGeneticsEscherichia coliGeneMicrobial Natural Products and BiosynthesisMicrobial Metabolism and ApplicationsGenomics and Phylogenetic Studies