Confronting PFAS persistence: enzymes catalyzing C–F bond cleavage

Studies of enzymes catalyzing carbon–fluorine (C–F) bond cleavage have focused largely on a limited number of native microbial hydrolases that are reactive with the natural product fluoroacetate. Driven by widespread interest in biodegrading commercial fluorinated compounds, many of which are known as per- and polyfluorinated alkyl substances (PFAS), it is necessary to identify and engineer new enzymes. For example, some hydrolases react with –CF₂– moieties, a common functionality in PFAS. Additional enzymatic C–F cleaving mechanisms catalyzed by reductases, lyases, and oxygenases have been identified via screening. Screening and evolving PFAS defluorination in bacteria is inhibited by the obligate release of toxic fluoride from C–F cleavage. Engineering greater fluoride tolerance in bacteria is a problem that must be solved in tandem with enzyme improvement.