[1S03m] 06. Enzyme Engineering/Enzymology - Part 1

11:00 AM - 11:15 AM JST(2:00 AM - 2:15 AM UTC)

[1ENZ-03] NHC-Mediated Radical Acylation Catalyzed by Thiamine- and Flavin-Dependent Enzymes

○Shunsuke Kato¹, Shuto Fujisawa², Yuto Adachi², Takashi Hayashi² (1. Kobe University (Japan), 2. The University of Osaka (Japan))

Keywords:

Biocatalysis,Enzyme,N-Heterocyclic Carbene,Radical reaction,Photocatalysis

Along with the significant progress of biotechnology, biocatalysis has been recently attracting increasing attention as a sustainable platform for manufacturing valuable chemicals. One of the main challenges associated with biocatalysis is to expand the catalytic repertoire of enzymes to meet the requirements of synthetic chemistry. In this context, our research group is working toward the discovery of novel enzymes capable of catalyzing abiotic chemical transformation by leveraging principles of organic chemistry.^1,2 In this presentation, we will report our recent research on discovering novel thiamine- and flavin-dependent enzymes capable of catalyzing N-heterocyclic carbene (NHC)-mediated radical acylation.³ Through a series of enzyme screenings, acetolactate synthase from Thermobispora bispora (TbALS) and its engineered variants were identified to exhibit promising catalytic activity toward abiotic radical acylation reactions of α-bromo carbonyl compounds. Notably, the TbALS variant has higher catalytic activity for small nonaromatic substrates despite forming less stable radical intermediates. Furthermore, the catalytic system of TbALS can be applied to photocatalytic reactions utilizing the photoredox properties of FAD. Nonbenzylic alkyl radicals generated from N-acyloxyphthalimides are efficiently converted into the corresponding dialkyl ketones under irradiation of a blue LED. Even though cross-coupling reactions between short-lifetime radicals are challenging reactions in organic chemistry, these findings highlight the utility of thiamine- and flavin-dependent enzymes for achieving selective cross-coupling reactions of short-lifetime radicals.
¹S. Kato et al. Angew. Chem. Int. Ed. 2023, 62, e202303764.
²S. Kato et al. Angew. Chem. Int. Ed. 2025, 64, e202511590.
³S. Kato et al. J. Am. Chem. Soc. 2025, 147, 14837-14844.