In natural world, sophisticated cascade reactions occur in compartmentalized organelles. However, simulating cascade processes in living systems remains problematic, and the drawbacks of enzymes, including dissatisfactory stability, reusability, and sensitivity in extreme microenvironments, have hampered further applications. Here, we report a confined multi-enzyme system in which MnFe metal-organic framework (MFM) is applied to encapsulate enzymes through shell-by-shell epitaxial-overgrowth in diverse compartments. MFM possessed excellent peroxidase-mimicking activity and biocompatibility, enabling it to serve not only as a reliable carrier for multiple enzymes, but also as a high-performance nanozyme in cascades. Compared with free enzymes, this system exhibited significantly improved bioactivity and environmental tolerance. On this basis, the confined multi-enzyme system was applied for selective α-amylase analysis in complicated fermentation specimens with a broad linear range (5-500 U·L