Mechanically Driven Enzyme Engineering: The New Frontier Beyond Chemistry

Enzymes, as natural biocatalysts, offer significant advantages, including high efficiency and substrate specificity, making them widely applicable in medicine, biology, agriculture, and food processing. However, their inherent structural instability often leads to deactivation under harsh conditions, such as elevated temperature, high pressure, extreme pH, or organic solvents. Additionally, difficulties in recovery and low reusability further limit their practical applications. To overcome these limitations, developing effective strategies to enhance enzyme activity and stability is of critical importance. Mechanical forces, applied through methods such as ultrasound, shear, or stretching, can modulate enzyme conformations and optimize substrate binding sites, thereby significantly boosting the catalytic performance while avoiding deactivation under adverse conditions. Furthermore, mechanical force-assisted encapsulation of enzymes within porous materials, such as metal-organic frameworks, covalent organic frameworks, and porous silicon, creates a protective microenvironment that enhances stability and broadens application prospects. This review systematically summarizes recent advances in the mechanical regulation of enzyme activity and discusses progress in the mechanoassisted encapsulation of enzymes in porous matrices. Finally, we address current challenges in elucidating the mechanisms underlying the mechanochemical regulation of enzyme conformation and activity, scaling up enzyme@porous material systems, and optimizing material-enzyme interfacial interactions, offering perspectives for future research.