Bird’s-Eye View: Current Understanding and Future Perspectives on the Biodefluorination of Per- and Polyfluoroalkyl Substances (PFAS)

• Biodefluorination and reaction pathways of emerging PFAS under aerobic and anaerobic conditions were reviewed. • Microorganisms responsible for PFAS biodefluorination were summarized. • The need to standardize testing protocols and improve biotransformation prediction methods was emphasized. • The potential of designing degradable fluorinated alternatives through benign-by-design principles were highlighted. Per- and polyfluoroalkyl substances (PFAS) have been extensively used in various industrial and manufacturing processes. These compounds pose potential risks to public health and ecosystems because of their persistence, bioaccumulation potential, and toxicity. To date, great efforts have been made to investigate the biotransformation of PFAS, while little is known about their biodefluorination behavior. A comprehensive understanding of biodefluorination mechanisms can not only aid in revealing the environmental fate and effects of these fluorinated chemicals but also advance the design of alternative structures with reduced persistence and environmental impact. In this review, we (1) systematically reviewed the biodefluorination pathways and transformation products of PFAS, with particular emphasis on emerging PFAS, under both aerobic and anaerobic conditions, (2) summarized the responsible microorganisms and enzymes involved, (3) provided critical perspectives on the need to standardize the testing protocol and to generalize the biotransformation prediction approaches, and (4) highlighted the potential of benign-by-design strategies in developing degradable fluorinated alternatives.