Improving the Enzymatic Cascade of Reactions for the Reduction of CO₂ to CH₃OH in Water: From Enzymes Immobilization Strategies to Cofactor Regeneration and Cofactor Suppression

The need to decrease the concentration of CO₂ in the atmosphere has led to the search for strategies to reuse such molecule as a building block for chemicals and materials or a source of carbon for fuels. The enzymatic cascade of reactions that produce the reduction of CO₂ to methanol seems to be a very attractive way of reusing CO₂; however, it is still far away from a potential industrial application. In this review, a summary was made of all the advances that have been made in research on such a process, particularly on two salient points: enzyme immobilization and cofactor regeneration. A brief overview of the process is initially given, with a focus on the enzymes and the cofactor, followed by a discussion of all the advances that have been made in research, on the two salient points reported above. In particular, the enzymatic regeneration of NADH is compared to the chemical, electrochemical, and photochemical conversion of NAD⁺ into NADH. The enzymatic regeneration, while being the most used, has several drawbacks in the cost and life of enzymes that suggest attempting alternative solutions. The reduction in the amount of NADH used (by converting CO₂ electrochemically into formate) or even the substitution of NADH with less expensive mimetic molecules is discussed in the text. Such an approach is part of the attempt made to take stock of the situation and identify the points on which work still needs to be conducted to reach an exploitation level of the entire process.