Biomimetic mineralization in layered ZIF-8 enables lipase immobilization for the synthesis of isosorbide dihexanoate.

Immobilization of lipases in metal-organic frameworks offers a potential route for developing robust biocatalysts for ester synthesis, but achieving efficient enzyme incorporation within structurally favorable hosts remains challenging. Here, we report a biomimetic mineralization strategy based on layered ZIF-8 for immobilization of Candida antarctica lipase B (CALB) and evaluate the resulting biocatalyst for the synthesis of isosorbide dihexanoate (SDH). Under optimized immobilization conditions, namely a CALB dosage of 1 mL, a Zn2+/2-methylimidazole molar ratio of 1:3, and a mineralization time of 6 h, CALB@mZIF-8 exhibited a protein loading of 201.50 mg/g and an activity of 36.71 U/g. The protein loading was higher than that obtained by conventional adsorption-based immobilization using ZIF-8. Applied to SDH synthesis in a 10 mL reaction system containing n-hexane (10%, v/v) as co-solvent, 0.4 g CALB@mZIF-8, an isosorbide-to-hexanoic acid molar ratio of 1:6, agitation at 150 rpm and 40 °C, the SDH yield reached 65.03%. Compared with free CALB, the immobilized biocatalyst exhibited enhanced operational stability and improved tolerance toward different reaction environments. These results demonstrate that layered ZIF-8 generated through biomimetic mineralization provides a tunable platform for lipase immobilization and represents a promising strategy for the synthesis of sterically hindered bio-based esters.