Beyond sequence and structure, enzymes in vivo operate within confined and crowded microenvironments that play a critical role in regulating catalytic performance. Cellular compartmentalization and macromolecular crowding can influence substrate diffusion, intermediate channeling, and intrinsic enzyme activity. Inspired by these biological systems, artificial confinement strategies using DNA, proteins, metal–organic frameworks, and polymer-based crowding agents have been developed to enhance enzyme stability and reusability. However, confinement often reduces enzyme activity due to mass transfer limitations or conformational constraints. Notably, cases of confinement-induced activation have been reported, yet the molecular mechanisms and general design principles remain poorly understood.
Recently, a research team of Associate Professor Yufei Cao of South China University of Technology and Professor Jun Ge of Tsinghua University revealed the mechanism of surface confinement enhancing the intrinsic catalytic activity of enzymes from two aspects of enthalpy effect and entropy effect, and provided a generalizable molecular mechanism and site screening strategy for the rational design of confined enzymes. The results were published in Chinese Journal of Catalysis (DOI: 10.1016/s1872-2067(25)64827-3 )
This study investigates the mechanism by which confinement affects enzyme intrinsic activity, using Bacillus subtilis lipase A (BSLA) as a model system through a combination of experimental approaches and theoretical calculations. Macromolecular crowding introduced by various polymers during BSLA catalysis leads to activity enhancement. QM/MM calculations indicate that confinement applied to the loop region of BSLA enhances intrinsic activity, arising from concurrent gains in enthalpic and entropic contributions. The confined lipase conformation promotes improved preorganization of the active site and increases the overlap of conformational state space between initial and transition states. And this confinement can be rationally engineered to construct advanced enzyme catalysts. A similar phenomenon is observed in PETase, suggesting potential universality of this effect. These findings shed light on the fine-tuning of confinements to enhance enzyme intrinsic activity and elucidate the regulatory mechanisms governing enzyme activity in confined or crowded conditions.
About the journal
Chinese Journal of Catalysis is co-sponsored by Dalian Institute of Chemical Physics, Chinese Academy of Sciences and Chinese Chemical Society, and it is currently published by Elsevier group. This monthly journal publishes in English timely contributions of original and rigorously reviewed manuscripts covering all areas of catalysis. The journal publishes Reviews, Accounts, Communications, Articles, Highlights, Perspectives, and Viewpoints of highly scientific values that help understanding and defining of new concepts in both fundamental issues and practical applications of catalysis. Chinese Journal of Catalysis ranks among the top six journals in Applied Chemistry with a current SCI impact factor of 17.7.
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Chinese Journal of Catalysis
Mechanism of confinement enhancing enzyme intrinsic activity
3-Feb-2026