Bacterial dehalogenases for organohalide and organofluorine remediation: Mechanistic insights, evidence gaps, and future relevance to GenX treatment.
Bacterial dehalogenase enzymes catalyze the cleavage of carbon-halogen bonds and play important roles in the microbial transformation of many halogenated contaminants. This review critically examines major classes of bacterial dehalogenases, including haloalkane dehalogenases, haloacid dehalogenases, fluoroacetate dehalogenases, reductive dehalogenases, and halohydrin dehalogenases, with emphasis on their structural features, catalytic residues, cofactor requirements, substrate specificity, and environmental controls on enzyme activity. Particular attention is given to the relevance and limitations of these enzymes for persistent, fluorinated contaminants, using hexafluoropropylene oxide dimer acid (HFPO-DA, commonly known as GenX) as a case study. Although microbial dehalogenation is well established for many chlorinated and brominated pollutants, direct enzymatic defluorination of GenX remains insufficiently demonstrated. Current evidence suggests that PFAS structure, including strong carbon-fluorine bonds, ether linkages, chain length, and terminal functional groups, strongly constrains microbial and enzymatic transformation. Therefore, this review distinguishes established dehalogenase-mediated organohalide degradation from emerging and still-unverified applications to GenX and related short-chain PFAS. Key research needs include identification of GenX-transforming microorganisms and enzymes, biochemical validation of reaction pathways, kinetic characterization, transformation-product toxicity assessment, enzyme engineering, computational modeling, and scalable hybrid treatment systems. By integrating mechanistic enzymology, environmental operating conditions, and sustainability considerations, this review provides a critical framework for evaluating whether dehalogenase-based approaches can contribute to future PFAS remediation strategies.