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Halogenases create diverse natural products by utilizing halide ions and are of great interest in the synthesis of potential pharmaceuticals and agrochemicals. An increasing number of halogenases discovered in microorganisms are annotated as flavin-dependent halogenases (FDHs), but their chemical reactivities are markedly different and the genomic contents associated with such functional distinction have not been revealed yet. Even though the reactivity and regioselectivity of FDHs are essential in the halogenation activity, these FDHs a