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

The utilization of carbon dioxide as a C-building block for the production of valuable chemicals has recently attracted much interest. Whereas chemical CO 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 -carboxylation of phenols catalyzed by metal-dependent -benzoic acid decarboxylases and (ii) the side-chain carboxylation of -hydroxystyrenes mediated by metal-independent phenolic acid decarboxylases. Just recently, the portfolio of bio-carboxylation reactions was complemented by (iii) the -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) CO 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.