Mechanistic Investigations of PoyD, a Radical S -Adenosyl- l -methionine Enzyme Catalyzing Iterative and Directional Epimerizations in Polytheonamide A Biosynthesis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of the American Chemical Society Année : 2018

Mechanistic Investigations of PoyD, a Radical S -Adenosyl- l -methionine Enzyme Catalyzing Iterative and Directional Epimerizations in Polytheonamide A Biosynthesis

Résumé

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing family of bioactive peptides. Among RiPPs, the bacterial toxin polytheonamide A is characterized by a unique set of post-translational modifications catalyzed by novel radical S-adenosyl-l-methionine (SAM) enzymes. Here we show that the radical SAM enzyme PoyD catalyzes in vitro polytheonamide epimerization in a C-to-N directional manner. By combining mutagenesis experiments with labeling studies and investigating the enzyme substrate promiscuity, we deciphered in detail the mechanism of PoyD. We notably identified a critical cysteine residue as a likely key H atom donor and demonstrated that PoyD belongs to a distinct family of radical SAM peptidyl epimerases. In addition, our study shows that the core peptide directly influences the epimerization pattern allowing for production of peptides with unnatural epimerization patterns.
Fichier principal
Vignette du fichier
ja7b08402.pdf (1.91 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-01939282 , version 1 (13-12-2023)

Identifiants

Citer

Aubérie Parent, Alhosna A. Benjdia, Alain A. Guillot, Xavier Kubiak, Clémence Balty, et al.. Mechanistic Investigations of PoyD, a Radical S -Adenosyl- l -methionine Enzyme Catalyzing Iterative and Directional Epimerizations in Polytheonamide A Biosynthesis. Journal of the American Chemical Society, 2018, 140 (7), pp.2469 - 2477. ⟨10.1021/jacs.7b08402⟩. ⟨hal-01939282⟩
219 Consultations
7 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More