Unusual O-H Activation-Initiated C-C Bond Cleavage Reaction by a Nonheme Fe Enzyme in Antifungal Nucleoside Biosynthesis.

ABSTRACT: Fe(II)- and α-ketoglutarate (α-KG)-dependent enzymes catalyze diverse reactions, generally initiated by Fe^IV=O mediated cleavage of C-H bonds with bond dissociation energies (BDE) of up to ∼100 kcal/mol. Here, we report the discovery of a novel reaction initiated by a significantly more challenging O-H bond cleavage (>100 kcal/mol). This activity was identified in PolD, an enzyme that regulates the sugar size in antifungal nucleoside biosynthesis by catalyzing the transformation of a bicyclic eight-carbon sugar substrate, 5'-amino-6'-hydroxy-octosyl acid 2'-phosphate (AHOAP), into a monocyclic six-carbon product, aminohexuronic acid 2'-phosphate (AHAP). Our studies demonstrate that PolD catalyzes a two-step reaction, in which AHOAP is first oxidized to 5'-amino-6'-keto-octosyl a

SUBMITTER: Du Y 

PROVIDER: S-EPMC12392984 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature