Role of reduced flavin in dehalogenation reactions

Halogenated organic compounds are extensively used in the cosmetic, pharmaceutical, and chemical industries. Several naturally occurring halogen-containing natural products are also produced, mainly by marine organisms. These compounds accumulate in the environment due to their chemical stability and lack of biological pathways for their degradation. However, a few enzymes have been identified that perform dehalogenation reactions in specific biological pathways and others have been identified to have secondary activities toward halogenated compounds. Various mechanisms for dehalogenation of I, Cl, Br, and F containing compounds have been elucidated. These have been grouped into reductive, oxidative, and hydrolytic mechanisms. Flavin-dependent enzymes have been shown to catalyze oxidative dehalogenation reactions utilizing the C4a-hydroperoxyflavin intermediate. In addition, flavoenzymes perform reductive dehalogenation, forming transient flavin semiquinones. Recently, flavin-dependent enzymes have also been shown to perform dehalogenation reactions where the reduced form of the flavin produces a covalent intermediate. Here, recent studies on the reactions of flavoenzymes in dehalogenation reactions, with a focus on covalent catalytic dehalogenation mechanisms, are described.