Characterization of a Dual Function Peptide Cyclase in Graspetide Biosynthesis.

ABSTRACT: Graspetides are a diverse family of ribosomally synthesized and post-translationally modified peptides with unique macrocyclic structures formed by ATP-grasp enzymes. Group 11 graspetides, including prunipeptin, feature both macrolactone and macrolactam cross-links. Despite the known involvement of a single ATP-grasp cyclase in the dual macrocyclizations of groups 5, 7, and 11 graspetides, detailed mechanistic insights into these enzymes remain limited. Here, we reconstructed prunipeptin biosynthesis from Streptomyces coelicolor using recombinant PruA and PruB macrocyclase. PruB exhibited kinetic behavior similar to other characterized graspetide cyclases, with a notably higher k_cat, likely due to utilization of an ATP-regeneration system. The X-ray crystal structu

SUBMITTER: Rubin GM 

PROVIDER: S-EPMC12117378 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature