Genome- and metabolome-guided discovery of marine BamA inhibitors revealed a dedicated darobactin halogenase - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cell Chemical Biology Année : 2023

Genome- and metabolome-guided discovery of marine BamA inhibitors revealed a dedicated darobactin halogenase

Résumé

Darobactins represent a class of ribosomally synthesized and post-translationally modified peptide (RiPP) antibiotics featuring a rare bicyclic structure. They target the Bam-complex of Gram-negative bacteria and exhibit in vivo activity against drug-resistant pathogens. First isolated from Photorhabdus species, the corresponding biosynthetic gene clusters (BGCs) are widespread among γ-proteobacteria, including the genera Vibrio, Yersinia, and Pseudoalteromonas (P.). While the organization of the BGC core is highly conserved, a small subset of Pseudoalteromonas carries an extended BGC with additional genes. Here, we report the identification of brominated and dehydrated darobactin derivatives from P. luteoviolacea strains. The marine derivatives are active against multidrug-resistant (MDR) Gram-negative bacteria and showed solubility and plasma protein binding ability different from darobactin A, rendering it more active than darobactin A. The halogenation reaction is catalyzed by DarH, a new class of flavin-dependent halogenases with a novel fold.
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Dates et versions

hal-04171205 , version 1 (26-07-2023)

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Nils Böhringer, Jil-Christine Kramer, Eugenio de la Mora, Leo Padva, Zerlina Wuisan, et al.. Genome- and metabolome-guided discovery of marine BamA inhibitors revealed a dedicated darobactin halogenase. Cell Chemical Biology, 2023, ⟨10.1016/j.chembiol.2023.06.011⟩. ⟨hal-04171205⟩
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