A non-conventional archaeal fluorinase identified by in silico mining catalyzes the fastest natural nucleophilic fluorination

Abstract

Fluorinases, the only enzymes known to catalyze the transfer of fluorine to an organic molecule, are essential biocatalysts for the sustainable synthesis of valuable organofluorines. However, the few fluorinases identified so far have low turnover rates that hamper biotechnological applications. Here, we isolated and characterized putative fluorinases retrieved from systematic in silico mining and identified a non-conventional archaeal enzyme from Methanosaeta sp. that mediates the highest fluorination rate reported to date. Furthermore, we demonstrate enhanced production of fluoronucleotides in vivo in a bacterial host engineered with this archaeal fluorinase, paving the way towards synthetic metabolism for efficient biohalogenations. Fastest biological SN2 fluorination