Enzyme-mediated biodegradation of per- and polyfluoroalkyl substances (PFAS): Challenges, opportunities, and future directions

• Cutting-edge enzymatic pathways for PFAS degradation are critically reviewed. • Engineered nanozymes offer robust, tunable, and reusable catalysts for PFAS degradation. • Co-immobilization, enzyme–photocatalyst hybrids, and microreactors drive next-generation PFAS remediation technologies. • Enzyme engineering and synthetic biology offer promising routes to design tailored PFAS degraders. • Integrating AI with experimental tools will revolutionize the discovery of novel PFAS-degrading enzymes. Per- and polyfluoroalkyl substances (PFAS) comprise a vast and chemically diverse group of synthetic fluorinated compounds that are widely used in industrial and consumer applications because of their hydrophobic and lipophobic properties. Characterized by their robust carbon–fluorine bonds, PFAS are highly resistant to environmental degradation, leading to widespread and persistent accumulation in ecosystems and organisms. This persistence and growing evidence of toxicity and bioaccumulation pose urgent ecological and public health challenges. Conventional treatment methods often fail to fully degrade PFAS, prompting growing interest in sustainable biocatalytic solutions. This review summarizes recent advances in enzyme-mediated PFAS degradation, focusing on the key oxidoreductases capable of cleaving recalcitrant C–F bonds. It also highlights the growing role of bioinspired nanozymes, particularly peroxidase- and laccase-mimicking nanomaterials, and discusses how their integration with synthetic supports enhances catalytic performance. Special emphasis is placed on co-immobilization strategies and the development of hybrid biocatalysts, which significantly improve enzyme stability, recyclability, and adaptability to harsh environmental conditions. Additionally, this review examines the synergistic application of computational tools, such as molecular dynamics, density functional theory (DFT), and machine learning, for enzyme engineering and mechanism elucidation. Together, these advancements have the potential to pave the way for scalable, selective, and highly efficient PFAS bioremediation technology.