Recent Progress and Challenges in Microbial Defluorination and Degradation for Sustainable Remediation of Fluorinated Xenobiotics

Fluorinated xenobiotics, such as per- and polyfluoroalkyl substances (PFAS), fluorinated pesticides, and pharmaceuticals, are extensively used across industries, but their extreme persistence, driven by the high carbon–fluorine (C–F) bond dissociation energy (~485 kJ/mol), poses serious environmental and health risks. These compounds have been detected in water, soil, and biota at concentrations from ng/L to µg/L, leading to widespread contamination and bioaccumulation. Traditional remediation approaches are often costly (e.g., EUR >100/m3 for advanced oxidation), energy-intensive, and rarely achieve complete degradation. In contrast, microbial defluorination offers a low-energy, sustainable alternative that functions under mild conditions. Microorganisms cleave C–F bonds through reductive, hydrolytic, and oxidative pathways, mediated by enzymatic and non-enzymatic mechanisms. Factors including electron donor availability and oxygen levels critically influence microbial defluorination efficiency. Microbial taxa, including bacteria, fungi, algae, and syntrophic consortia, exhibit varying defluorination capabilities. Metagenomic and microbial ecology studies continue to reveal novel defluorinating organisms and metabolic pathways. Key enzymes, such as fluoroacetate dehalogenases, cytochrome P450 monooxygenases, reductive dehalogenases, peroxidases, and laccases, have been characterised, with structural and mechanistic insights enhancing the understanding of their catalytic functions. Enzyme engineering and synthetic biology tools now enable the optimisation of these enzymes, and the design of microbial systems tailored for fluorinated compound degradation. Despite these advances, challenges remain in improving enzyme efficiency, broadening substrate specificity, and overcoming physiological constraints. This review emphasises the emerging promise of microbial defluorination as a transformative and green solution, uniquely integrating recent multidisciplinary findings to accelerate the development of sustainable microbial defluorination strategies for effective remediation of fluorinated xenobiotics.