Specific Enzymatic Halogenation—From the Discovery of Halogenated Enzymes to Their Applications In Vitro and In Vivo

Abstract During the last 20 years, focus has shifted from haloperoxidases to flavin‐dependent and non‐heme‐iron halogenases because of their proven involvement in the biosynthesis of halogenated metabolites in different organisms and the regioselectivity of their reactions. During the first 10–12 years, the main research topics were the detection of halogenases as well as the elucidation of three‐dimensional structures and reaction mechanisms. This Review mainly deals with studies on halogenating enzymes published between 2010 and 2015. It focusses on the elucidation of the involvement of halogenating enzymes in halometabolite biosynthesis, application of halogenases in in vivo and in vitro systems, in vivo modification of biosynthetic pathways in bacteria and plants, improvement of enzyme stability, broadening of substrate specificity, and the combination of biocatalysis with chemical synthesis to produce new compounds.