Biologically generated carbon dioxide: nature's versatile chemical strategies for carboxy lyases

Covering: up to 2019Metabolic production of CO₂ is natural product chemistry on a mammoth scale. Just counting humans, among all other respiring organisms, the seven billion people on the planet exhale about 3 billion tons of CO₂ per year. Essentially all of the biogenic CO₂ arises by action of discrete families of decarboxylases. The mechanistic routes to CO₂ release from carboxylic acid metabolites vary with the electronic demands and structures of specific substrates and illustrate the breadth of chemistry employed for C-COO (C-C bond) disconnections. Most commonly decarboxylated are α-keto acid and β-keto acid substrates, the former requiring thiamin-PP as cofactor, the latter typically cofactor-free. The extensive decarboxylation of amino acids, e.g. to neurotransmitter amines, is synonymous with the coenzyme form of vitamin B₆, pyridoxal-phosphate, although covalent N-terminal pyruvamide residues serve in some amino acid decarboxylases. All told, five B vitamins (B₁, B₂, B₃, B₆, B₇), ATP, S-adenosylmethionine, manganese and zinc ions are pressed into service for specific decarboxylase catalyses. There are additional cofactor-independent decarboxylases that operate by distinct chemical routes. Finally, while most decarboxylases use heterolytic ionic mechanisms, a small number of decarboxylases carry out radical pathways.