Integration of Enzyme and Covalent Organic Frameworks: From Rational Design to Applications

Manufacturing is undergoing profound transformations, among which green biomanufacturing with low energy consumption, high efficiency, and sustainability is becoming one of the major trends. However, enzymes, as the "core chip" of biomanufacturing, are often handicapped in their application by their high cost, low operational stability, and nonreusability. Immobilization of enzymes is a technology that binds or restricts enzymes in a certain area with solid materials, allows them to still carry out their unique catalytic reaction, and allows them to be recycled and reused. Compared with free enzymes, immobilized enzymes boast numerous advantages such as enhanced storage stability, ease of separation, reusability, and controlled operation. Currently, commonly used supports for enzyme immobilization (e.g., mesoporous silica, sol-gel hydrogels, and porous polymer) can effectively improve enzyme stability and reduce product inhibition. However, they still face drawbacks such as potential leaching or conformational change during immobilization and poor machining performance. Especially, most enzyme carrier solid materials possess disordered structures, inevitably introducing deficiencies such as low loading capacity, hindered mass transfer, and unclear structure-property relationships. Additionally, it remains a notable challenge to meticulously design immobilization systems tailored to the specific characteristics of enzyme/reaction. Therefore, there is a significant demand for reliable solid materials to overcome the above challenges. Crystalline porous materials, particularly covalent organic frameworks (COFs), have garnered significant interest as a promising platform for immobilizing enzymes due to their unique properties, such as their crystalline nature, high porosity, accessible active sites, versatile synthetic conditions, and tunable structure. COFs create a stabilizing microenvironment that protects enzymes from denaturation and significantly enhances reusability. Nevertheless, some challenges still remain, including difficulties in loading large enzymes, reduced enzyme activities, and the limited functionality of carriers. Therefore, it is essential to develop innovative carriers and novel strategies to broaden the methods of immobilizing enzymes, enabling their application across a more diverse array of fields.The integration of enzymes with advanced porous materials for intensified performance and diverse applications is still in its infancy, and our group has done a series of pioneering works. This Account presents a comprehensive overview of recent research progress made by our group, including (i) the development of innovative enzyme immobilization strategies utilizing COFs to make the assembly and integration of enzymes and carriers more effective; (ii) rational design and construction of functional carriers for enzyme immobilization using COFs; and (iii) extensions of immobilized enzyme applications based on COFs from industrial catalysis to biomedicine and chiral separation. The integration of enzymes with functional crystalline materials offers mutual benefits and results in a performance that surpasses what either component can achieve individually. Additionally, immobilized enzymes exhibit enhanced functionality and intriguing characteristics that differ from those of free enzymes. Consistent with our research philosophy centered on integration, platform development, and engineering application, this Account addresses the critical challenges associated with enzyme immobilization using COFs while extending the applications of COFs and proposing future design principles for biomanufacturing and enzyme industry.