Structure-Guided Mechanistic Investigation of Stereochemical Inversion during the Octose Formation Catalyzed by an Atypical Transaldolase AprG in the Biosynthesis of Apramycin.

ABSTRACT: Transaldolases are essential enzymes across all life domains, facilitating the exchange of aldol fragments in metabolic processes. AprG, a transaldolase in the apramycin biosynthetic pathway, catalyzes the incorporation of C7' and C8' moieties into the bicyclic octose core. Unlike canonical transaldolases, the AprG product exhibits unique stereochemical inversion, whose mechanism remains unclear. Here, by taking snapshots of AprG at different stages of the reaction, we identified active site residues essential for each reaction step. Strikingly, we discovered a 7'-epimer of the AprG product, directly implicating this inversion in the enzyme's mechanism and uncovering a key aspect of product inhibition. This unexpected epimer sheds a light on the stereochemical plasticity of transaldolases.

SUBMITTER: Kim W 

PROVIDER: S-EPMC12377196 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature