Although it has become widely known over the years that metal cofactors are the primary requirement for functional CA, Hirakawa and his coworkers recently defied this notion. They reported a metal-independent CA, termed 'COG4337,' which can catalyze the CO2 hydration with roughly the same efficiency as other metal-containing CA. Genes expressing the enzyme bacteria. They further isolated and crystallized two 'COG4337' enzymes, Bn86287 and all2909, from chlorarachniophyte alga (Bigelowiella natans) and cyanobacterium (Anabaena sp. PCC7120). Thus, these two-variant become the first evident of known CA, which can perform CO2 hydration in metal restrictive conditions. Another notable feature of this metalfree CA is that, unlike most metal-containing CA, it cannot perform the reverse reaction, which is dehydration of HCO3 -. Additionally, Gomez et al. recently provided evidence of metalindependent CA activity in crotonyl-CoA carboxylase/reductase using infrared spectroscopy. Given the abundance of metal-free CA among bacteria and microalgae, and their inability to catalyze the reverse dehydration of HCO3 -into CO2, this class of enzyme may play a significant role in reducing global CO2 accumulation. Note that both CO2 molecules are derived from the same crystallographic geometry. In both figures, the electrostatic potential map on the molecular surface, with a charge range of +3 to -3, was generated using the ABPS plugin incorporated in PYMOL software. Color codes: red for negative, blue for positive, and white for neutral electrostatic potential areas.