Advances in Dehalogenase Biocatalysis: Mechanisms, Engineering, and Industrial Perspectives

Halogenated organic compounds represent a significant environmental hazard due to their persistence and resistance to degradation. Dehalogenases, enzymes that efficiently remove halogens, offer versatile solutions for environmental remediation, green synthesis, and biocatalysis. For instance, LinB dehalogenates β-HCH to pentachlorocyclohexanol, and HHDH catalyzes epoxide ring-opening reactions to synthesize various β-substituted alcohols using different nucleophilic reagents. Recent advances elucidate their molecular mechanisms and enable sophisticated engineering. In this review, we summarize current advances in dehalogenase research, spanning their evolutionary origins, catalytic mechanisms, and classification across major enzyme families. We further highlight recent advances in enzyme engineering and AI-assisted design that are enhancing stability, broadening substrate scope, and unlocking novel catalytic functions. Finally, we discuss emerging opportunities for deploying engineered dehalogenases in bioremediation and green chemical synthesis. Together, these developments are transforming dehalogenases into efficient biocatalysts, offering powerful tools for environmental remediation and green chemistry.