Diverse models of cavity engineering in enzyme modification: Creation, filling, and reshaping

Most enzyme modification strategies focus on designing the active sites or their surrounding structures. Interestingly, a large portion of the enzymes (60%) feature active sites located within spacious cavities. Despite recent discoveries, cavity-mediated enzyme engineering remains crucial for enhancing enzyme properties and unraveling folding-unfolding mechanisms. Cavity engineering influences enzyme stability, catalytic activity, specificity, substrate recognition, and docking. This article provides a comprehensive review of various cavity engineering models for enzyme modification, including cavity creation, filling, and reshaping. Additionally, it also discusses feasible tools for geometric analysis, functional assessment, and modification of cavities, and explores potential future research directions in this field. Furthermore, a promising universal modification strategy for cavity engineering that leverages state-of-the-art technologies and methodologies to tailor cavities according to the specific requirements of industrial production conditions is proposed.