Carbonic anhydrase (CA) is an essential enzyme for carbon-based life and is ubiquitous in all biological kingdoms. This superfamily of enzymes is known to catalyze the reversible conversion of CO2 and HCO3 -using a water molecule (CO2 + H2O ↔ HCO3 -+ H + ). Although carbonic anhydrase catalyzes a simpler reaction, it is crucial for several biologically relevant processes, e.g., respiration, photosynthesis, pH control, gluconeogenesis, lipogenesis, and many more. Furthermore, CA is proposed as a key enzyme for CO2 fixation, making its chemistry fundamental importance to green catalysis. So far, eight different classes (α, β, γ, δ, ζ, η, θ, and ι) of CA have been discovered, which are evolved convergently to perform a specific function. As a result, CA is also considered as the textbook example of convergent evolution. Despite having several numbers of classes, they share a few common features. The most prominent similarity within all categories is the presence of a metal cofactor at the active site. And among all, the Zn 2+ is the most prevalent metal cofactor, but several other metal ions, including Fe 2+ , Cd 2+ , Mn 2+ , and Co 2+ , are also observed. In the case of Zn 2+ containing CA, the metal cofactor tetrahedrally binds with three His residues and a hydroxide (OH -) ion (cf. Scheme 1). The active site architecture of CA exhibits a unique structural feature, where it is divided into two distinct halves: approximately half of the residues are hydrophilic, while the other half are hydrophobic in nature (cf. Figure ). This division is distinguished by the presence of a bulky Phe residue at the center, which creates a 'bipolar' configuration within the active site (cf. Figure ). For metal-containing CA, it is well known that the hydrophobic half of the active site captures CO2 and directs it to the hydrophilic catalytic site (cf. Figure ), where it completes its catalysis to HCO3 -. Thus, it shows the crucial role of the 'bipolar' nature of the active site geometry in facilitating the catalytic function of metal-containing CA.