To address these limitations, we capitalised on a new-to-nature enzymatic mechanism to discover and evolve Fe enzymes for asymmetric C-F bond formation. In 2021, our group implemented metalloredox radical biocatalysis as a general means to develop unnatural biocatalytic radical reactions (Fig. ) . In our prior study, we engineered P450 enzymes as atom transfer radical cyclases to catalyse stereocontrolled bromine atom transfer . Contemporaneous to our studies, elegant work from the Huang laboratory led to highly efficient nonheme Fe azidases using a radical relay strategy . Parallel to the study from the Huang group, we independently posited that if we could concurrently generate a transient carbon-centred radical and a Fe(III)-F intermediate through a metalloredox atom transfer mechanism (Figs. and), we would be able to bypass the energetically demanding fluoride binding step as well as the ferryl intermediate formation for radical generation, thus directly interrogating the feasibility of C-F bond formation with Fe-dependent enzymes. Specifically, inspired by non-stereoselective small-molecule Fe catalysis , our proposal for the biocatalytic asymmetric fluorination using Fe enzymes is outlined in Fig. . Starting from the N-fluoroamide (I), fluorine atom transfer to the Fe(II) enzyme (II) would lead to a nitrogen-centred radical (i.e., amidyl radical III) and an Fe(III)-F species (IV). Due to the high N-H bond dissociation enthalpy (BDE (N-H) = 103.7 kcal/mol as determined by our DFT calculations (see the Supplementary Information for details), rapid 1,5-hydrogen atom transfer (1,5-HAT) of III would lead to a new carbon-centred radical (V). At this stage, stereoselective radical rebound of V with the enzymatic Fe(III)-F intermediate IV would lead to C-F bond formation VI and convert the ferric enzyme to its ferrous state, thereby completing the catalytic cycle. If successfully implemented, this work would lead to the first examples of metalloenzymes capable of forming C-F bonds. Furthermore, it would provide a rare example of highly enantioselective C(sp 3 )-H fluorination using an open-shell mechanism.