A Selenium-for-Oxygen Swapping Reaction Catalyzed by the Radical S -Adenosyl Methionine Enzyme AbmM
Year: 2025
Type: article
Abstract: Selenium is an essential element to organisms; however, few enzymes are known to catalyze the carbon–selenium bond formation. While several carbon–sulfur bond-forming enzymes have been engineered to install carbon–selenium bonds by using paired electron chemistry, the potential of utilizing radical chemistry to facilitate C–Se bond formation is underdeveloped. Herein, the native sulfur-inserting radical S -adenosyl methionine (SAM) enzyme AbmM involved in the biosynthesis of albomycin δ 2 is shown to catalyze a selenium-for-oxygen swapping reaction converting the furanose of cytidine 5′-diphosphate to a 4′-hydroxy-4′-selenofuranose diphosphate. The dephosphorylated 4′-seleno product can be further processed by downstream biosynthetic enzymes AbmG and AbmH to yield a 4′-selenoheptose nucleoside. These results establish an enzymatic approach to synthesize 4′-seleno sugars in a radical-mediated manner and provide a likely route to prepare selenium-containing analogues of albomycin δ 2 for drug discovery. This work also demonstrates that [Fe 4 Se 4 ] clusters can support radical SAM redox chemistry and that the radical SAM cluster in AbmM can function as the chalcogen donor.
DOI: 10.1021/jacs.5c16873
Authors: Ziyang Zheng, Yu-Hsuan Lee, Hung-wen Liu
Institution: The University of Texas at Austin
Language: English
Subfield: Toxicology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4415675014