Si Liu, Peiji Deng, Qianfan Chen, Qijun Sun, Yanhan Wang, Hongyu Shi, Kang Liang
Reticular materials, including metal-organic frameworks (MOFs), covalent organic frameworks (COFs), and hydrogen-bonded organic frameworks (HOFs), have emerged as a promising platform for enzyme immobilization due to their large surface area, tunable porosity, and diverse functional sites. However, the performance of enzymes encapsulated within these frameworks is frequently compromised, which primarily arises from spatial confinement, unfavorable interactions, and altered microenvironments that impair the native structure and dynamics of enzymes. A comprehensive understanding of the molecular events underlying enzyme encapsulation within frameworks is pivotal for the development of effective strategies to boost biocatalyst activity, thus unlocking its full potential in practical applications. Based on cutting-edge examples, this review summarizes these approaches from the multiscale aspect, encompassing material tuning at the nano/macro level, interface design at the molecular interface level, and protein surface engineering at the molecular level. Meanwhile, the differences in improving the enzyme activity among MOFs-, COFs-, and HOFs-based biocomposites are highlighted. Additionally, the regulations derived from the nano-bio effect can achieve the nanobiohybrids with customized, non-native biocatalytic functions, which are systematically discussed. Finally, the current challenges and opportunities in heterogeneous biocatalysts based on reticular chemistry are underscored, charting a path toward advanced designs and their translation into impactful real-world applications.