We show that an enzyme maintains its biological function under a wider range of conditions after being embedded in metal-organic framework (MOF) microcrystals via a de novo approach. This enhanced stability arises from confinement of the enzyme molecules in the mesoporous cavities in the MOFs, which reduces the structural mobility of enzyme molecules. We embedded catalase (CAT) into zeolitic imidazolate frameworks (ZIF-90 and ZIF-8), and then exposed both embedded CAT and free CAT to a denature reagent (i.e., urea) and high temperatures (i.e., 80 degrees C). The embedded CAT maintains its biological function in the decomposition of hydrogen peroxide even when exposed to 6 M urea and 80 degrees C, with apparent rate constants k(obs) (s(-1)) of 1.30 X 10(-3) and 1.05 x 10(-3), respectively, while free CAT shows undetectable activity. A fluorescence spectroscopy study shows that the structural conformation of the embedded CAT changes less under these denaturing conditions than free CAT.