Halogenases and dehalogenases: mechanisms, engineering, and applications

-adenosylmethionine (SAM)-dependent) types, facilitate precise C-X bond formation under mild conditions. Recent advances in protein engineering, such as the modification of tryptophan halogenases and fluorinases, have greatly expanded the repertoire and efficiency of biocatalytic halogenation, enabling the production of new-to-nature compounds for synthetic biology applications. In parallel, dehalogenases, ranging from reductive to hydrolytic and oxidative enzymes, play crucial roles in removing halogens from persistent pollutants, thereby supporting effective bioremediation and environmental detoxification. This review summarizes recent progress in enzyme discovery, mechanistic elucidation, protein engineering, and applied synthetic biology, with a focus on the integration of halogenases and dehalogenases into scalable platforms for both biosynthetic and remediation. Continued research aimed at improving enzyme stability, substrate scope, and operational robustness will be critical to fully realizing the industrial and environmental potential of these versatile biocatalysts.