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Enzymatic trans-halogenation enables radiolabeling under mild and aqueous conditions, but rapid reactions are desired. We developed a coupled chlorinase-fluorinase system for rapid trans-halogenation. Notably, the chlorinase shares a substrate tolerance with the fluorinase, enabling these two enzymes to cooperatively produce 5'-fluorodeoxy-2-ethynyladenosine (5'-FDEA) in up to 91.6% yield in 1 h.

A coupled chlorinase–fluorinase system with a high efficiency oftrans-halogenation and a shared substrate tolerance