Implications of non-native metal substitution in carbonic anhydrase - engineered enzymes and models

The enzyme carbonic anhydrase has been intensely studied over decades as a means to understand the role of zinc in hydrating CO₂. The naturally occurring enzyme has also been immobilized on distinct heterogeneous platforms, which results in a different hybrid class of catalysts that are useful for the adsorption and hydration of CO₂. However, the reusability and robustness of such natural and immobilized systems are substantially affected when tested under industrial conditions, such as high temperature and high flow rate. This led to the generation of model systems in the form of metal-coordination complexes, metal-organic frameworks, metallo-peptide self-assembled supramolecules and nanomaterials that mimic the primary, and, to some extent, secondary coordination sphere of the active site of the natural carbonic anhydrase enzymes. Furthermore, the effects of zinc-substitution by other relevant transition metals in both the naturally occurring enzymes and model systems has been reported. It has been observed that some other transition metal ions in the active site of carbonic anhydrase and its models can also accomplish similar activity, established by various reaction probes and ideas. Herein, we present a comprehensive highlight about substituting zinc in the active site of the modified enzymes and its biomimetic model systems with non-native metal ions and review how they affect the structural orientation and reactivity towards CO₂ hydration. In addition, the utility of artificially engineered carbonic anhydrases towards a number of non-natural reactions is also discussed.