Flavin‐Dependent Halogenases: Emerging Enzymes and New Functions

Abstract Flavin‐dependent halogenases (FDHs) are remarkable biocatalysts because they can catalyze the precise installation of carbon‐halogen (C─X) bonds in organic compounds due to their specific catalytic features. Recently, many notable FDHs with potential applications in diverse and challenging synthetic chemistry and pharmaceutical biosynthesis processes have been reported. Various new FDHs, especially single‐component halogenases with novel functions and mechanisms, can catalyze the halogenation of diverse substrate scaffolds beyond just simple aromatic halogenation. This concept article discusses recent findings obtained over the past 5 years for novel FDHs and highlights important structural and mechanistic insights into single‐component FDH catalysis. Furthermore, new approaches for identifying non‐native halogenases are discussed, and a showcase of redesigned FDHs with expanded catalytic functions is presented.