Biocatalytic cascades driven by enzymes encapsulated in metal–organic framework nanoparticles

Biocatalytic transformations in cells, such as enzyme cascades, involve complex networks proceeding in spatially confined microenvironments. Here, inspired by nature, we demonstrate effective biocatalytic cascades by the encapsulation of two or three enzymes, or enzyme/cofactor components, in zeolitic imidazolate framework-8 metal–organic framework nanoparticles (ZIF8-NMOFs) that act as nanoreactors. The integration of the two-enzyme system (glucose oxidase and horseradish peroxidase) or three-enzyme system (β-galactosidase, glucose oxidase and horseradish peroxidase) in the NMOFs leads to 7.5-fold and 5.3-fold enhancements in the activity of the catalytic cascades, respectively, compared with the bulk mixture of the catalysts in solution. In addition, the encapsulation of alcohol dehydrogenase, NAD+–polymer and lactate dehydrogenase in the NMOFs yields a coupled biocatalytic cascade involving coupled NAD+-dependent enzymes, leading to the catalytic reduction of pyruvic acid to lactic acid by ethanol. High activity and stability of enzyme cascades are key to their biotechnological application. Here, Willner and co-workers demonstrate that encapsulation in metal–organic framework nanoparticles can improve these features for two- and three-enzyme, as well as NAD+-dependent, cascades.