Dynamic constitutional frameworks composed of cross-linked networks of imine-exchanging components have been generated and applied to the establishment of optimal microenvironments for carbonic anhydrase (CA) in aqueous solution. In response to the dynamic recomposition process, the enzyme showed distinct differential preferences for interchanging and incorporation of the amine functionalities, which were furthermore in good correlation with their inverse activation effects of CA. The results demonstrated surface-directed selection of the enzyme environment, where amines with lower enzyme-directed incorporation ratio possess higher activation effects, leading to a strategy of self-optimization of the enzyme microenvironment for better catalytic performances.