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Nat. Prod. Rep., Nov 03 2025, | https://doi.org/10.1039/d5np00055f Halogenases and dehalogenases: mechanisms, engineering, and applications

Jing Luo,^a, Na Li,^a, Jia Wang,^a, Yaojie Gao,^a, Hongzhi Tang,^*a, Linquan Bai,^*a, Sang Yup Lee^*bcd and Yaojun Tong^*a

^aState Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
^bMetabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
^cBioProcess Engineering Research Center, KAIST, Daejeon 34141, Republic of Korea
^dGraduate School of Engineering Biology, KAIST, Daejeon 34141, Republic of Korea

*Corresponding authors

Abstract

Halogenated organic compounds (HOCs) are essential building blocks in pharmaceuticals, agrochemicals, and advanced materials. However, their conventional chemical synthesis often relies on hazardous reagents and generates significant environmental waste. Harnessing nature's solutions, halogenases and dehalogenases offer selective, eco-friendly alternatives for the biosynthesis and degradation of HOCs. Halogenases, including electrophilic (e.g., haloperoxidases, flavin-dependent), radical (α-ketoglutarate-dependent), and nucleophilic (S-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.

논문정보

형식Review Paper
게재일2025년 11월 (BRIC 등록일 2025-11-04)
연구진국내(교신)+국외 연구진
분야 생명과학 > 생물공학

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