Characterizing Y224 conformational flexibility in FtmOx1-catalysis using ¹⁹F NMR spectroscopy.

ABSTRACT: α-Ketoglutarate-dependent non-haem iron (αKG-NHFe) enzymes play a crucial role in natural product biosynthesis, and in some cases exhibiting multifunctional catalysis capability. This study focuses on αKG-NHFe enzyme FtmOx1, which catalyzes endoperoxidation, dealkylation, and alcohol oxidation reactions in verruculogen biosynthesis. We explore the hypothesis that the conformational dynamics of the active site Y224 confer the multifunctional activities of FtmOx1-catalysis. Utilizing Y224-to-3,5-difluorotyrosine-substituted FtmOx1, produced via the amber codon suppression method, we conducted ¹⁹F NMR characterization to investigate FtmOx1's structural flexibility. Subsequent biochemical and X-ray crystallographic analyses provided insights into how specific conformations of

SUBMITTER: Wang X 

PROVIDER: S-EPMC11629144 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature