Thiamine diphosphate–dependent carboligases: a new frontier for methanol bioconversion

Photoelectrocatalytic technology enables the efficient conversion of CO₂, a key contributor to the greenhouse effect. Owing to its high reducibility, abundant reserves, and low cost, methanol is considered an ideal carbon substrate for biomanufacturing. Although some natural methylotrophic microorganisms can natively metabolize and utilize methanol, their extremely low utilization and conversion efficiencies are major deterrents. Thiamine diphosphate (ThDP)-dependent carboligases provide methanol with more efficient and diverse conversion pathways through their unique C–C bond formation mechanisms. This review discusses the beneficial role of ThDP-dependent carboligases in methanol bioconversion. Furthermore, we analyze the limitations of these carboligases in this process and propose feasible solutions to promote the development of third-generation biomanufacturing using one-carbon materials.