Bioinspired nanozymes are promising in mimicking natural processes and developing function-enhanced architectures. However, constructing artificial enzyme systems with catalytic efficiencies rivaling that of natural enzymes in a minimal principle is challenging. Herein, we report the construction of minimal metallo-nanozymes through amino acid coordinated self-assembly by using amino acid derivatives and zinc (II) ions as the building blocks, reminiscent of the components of the catalytic architectures in natural hydrolases. The obtained metallonanozymes possess high and robust activity comparable to that of natural lipase in catalytically hydrolyzing phenyl acetate. In addition, catalytic performance of the metallo-nanozymes can be facilely optimized by changing the ratio between the building blocks and the introduction of additional biomolecules. The metallonanozymes also show catalytic activity in producing acetylsalicylic acid through the hydrolyzation of a prodrug, benorilate. This work highlights the minimal principle and excellent catalytic performance of stable metallonanozymes, opening up immense opportunities in the development of highly efficient nanozymes and catalytic prodrug conversion.