Over the past decade, groundbreaking studies on unnatural biocatalysis have transformed the biochemical landscape of natural enzymes to encompass biocatalytic reactions that were never previously encountered in nature . Recently, biocatalysis researchers have discovered a range of useful unnatural enzymatic activities, particularly asymmetric free radical transformations with metalloenzymes as well as nicotinamide- , flavin- , and pyridoxal phosphate (PLP) dependent enzymes. Together, these efforts substantially expanded the reaction territory of enzyme catalysis and furnished powerful tools for asymmetric synthesis. Despite these notable advances, new-to-nature enzymatic C-F bond formation has long eluded the biocatalysis community. The dearth of fluorination enzymatic functions is in stark contrast to the ubiquity of organofluorine compounds in the pharmaceutical and agrochemical industries, as the incorporation of fluorine into organic compounds can often lead to improved bioavailability, enhanced metabolic stability, and desirable protein binding affinity . In light of the broad utility of organofluorine compounds, particularly those possessing a fluorinated stereogenic centre , fluorine biocatalysis and fluorine synthetic biology have long captivated synthetic chemists and synthetic biologists. Among the various fluorination methods , biocatalytic enantioselective C(sp )-H fluorination would be particularly valuable , as only a handful of chemocatalytic asymmetric C(sp )-H fluorination methods are available to non-enolate systems , further highlighting the challenge in imposing stereocontrol over fluorination processes. Among these, highly enantioselective C(sp 3 )-H fluorination using a free radical mechanism 26 is particularly challenging. To date, fluorinases discovered from bacteria and archaea represent the only natural enzyme class capable of incorporating a fluorine atom to organic substrates (Fig. ). Using a simple bimolecular nucleophilic substitution (SN2) mechanism, natural fluorinases catalyse the conversion of S-adenosylmethionine (SAM) to 5'-fluoro-5'-deoxyadenosine (5'-FDA), giving rise to fluorometabolites through downstream biosynthetic pathways. On the other hand, an array of a-ketoglutarate (aKG)-dependent nonheme Fe enzymes has been discovered and engineered to facilitate C-H (pseudo)halogenation reactions , including chlorination , bromination , azidation and nitration (Fig. ). Mechanistically, these nonheme Fe enzymes generate a carbon-centred radical by hydrogen atom transfer (HAT) via the intermediacy of (X)Fe(IV)=O (X = (pseudo)halide). The incipient carbon-centred radical subsequently undergoes halogen atom transfer with the Fe(III)-X intermediate, leading to C-H halogenated products . Despite extensive studies, to date, converting nonheme Fe halogenases to fluorinases has not been met with success. Several mechanistic rationales, including the low binding affinity of Fe enzymes toward the aqueous fluoride ion (F -) owing to the high hydration energy of F -38 , challenging formation of the ferryl intermediate from the putative Fe(II)-F species, and difficulties steering the radical rebound activity toward the Fe(III)-F over Fe(III)-OH moiety, have been postulated to account for this long-standing challenge.