Non-Oxidative Enzymatic (De)Carboxylation of (Hetero)Aromatics and Acrylic Acid Derivatives

The utilization of carbon dioxide as a C₁-building block for the production of valuable chemicals has recently attracted much interest. Whereas chemical CO₂ fixation is dominated by C-O and C-N bond forming reactions, the development of novel concepts for the carboxylation of C-nucleophiles, which leads to the formation of carboxylic acids, is highly desired. Beside transition metal catalysis, biocatalysis has emerged as an attractive method for the highly regioselective (de)carboxylation of electron-rich (hetero)aromatics, which has been recently further expanded to include conjugated α,β-unsaturated (acrylic) acid derivatives. Depending on the type of substrate, different classes of enzymes have been explored for (i) the ortho-carboxylation of phenols catalyzed by metal-dependent ortho-benzoic acid decarboxylases and (ii) the side-chain carboxylation of para-hydroxystyrenes mediated by metal-independent phenolic acid decarboxylases. Just recently, the portfolio of bio-carboxylation reactions was complemented by (iii) the para-carboxylation of phenols and the decarboxylation of electron-rich heterocyclic and acrylic acid derivatives mediated by prenylated FMN-dependent decarboxylases, which is the main focus of this review. Bio(de)carboxylation processes proceed under physiological reaction conditions employing bicarbonate or (pressurized) CO₂ when running in the energetically uphill carboxylation direction. Aiming to facilitate the application of these enzymes in preparative-scale biotransformations, their catalytic mechanism and substrate scope are analyzed in this review.