Photochemically Driven Biocatalysis of Halogenases for the Green Production of Chlorinated Compounds

Flavin‐dependent tryptophan halogenases provide a regioselective access to chlorinated and brominated indole derivatives under mild conditions. Application of the halogenase requires a regeneration system for the reduced flavin cofactor FADH 2 , which is usually achieved by enzymatic or chemical reactions. We employed the halogenase PyrH from Streptomyces rugosporus as a model system to establish a photochemical approach by using blue light and a reductant for regeneration of FADH 2 . In contrast to previous light‐driven biocatalysis using flavin, the conversion of enzyme‐bound flavin in our approach suppresses futile cycles, in which the free flavin reacts with oxygen under generation of H 2 O 2 . Within 25 h, 70 % of 0.5 m m tryptophan was converted regioselectively to 5‐chlorotryptophan. Our regeneration system paves the way for production of chlorinated compounds by applying only light, halide salt, air, and a cheap sacrificial electron donor in aqueous solution.