Pyruvate-formate lyase and beyond

Pyruvate-formate lyases (PFLs) are crucial catalysts that employ both a core enzyme and an activating enzyme to facilitate the conversion of pyruvate to formate and acetyl-CoA, as well as its reverse reaction, in anaerobic and microaerobic prokaryotes. Because of the importance in formate metabolism in microorganisms, PFLs have had many potential applications in biological synthesis, environmental improvement, and medical treatment. Furthermore, formate is a direct product of CO₂ reduction via the catalysis of formate dehydrogenase or chemical conversion, thus suggesting potential applications for PFLs in CO₂ utilization by in vivo cascades or in vitro chemo-enzymatic reaction sequences, which, however, has not received attention to date. In this review, we summarize recent progress in the characterization and functionality of PFLs and consider potential applications of these enzymes. The directions of future research and possible challenges to the application of PFLs are also discussed.