Abstract: Provided herein is a stabilized DNase I polypeptide containing a non-standard amino acid that maintains enzymatic activity even under harsh conditions, such as reducing environments. The stabilized DNase I polypeptide has enzymatic activity in reducing environments that is higher than a corresponding DNase I polypeptide without the non-standard amino acids under the same conditions. Also provided herein are polynucleotides encoding the stabilized DNase I polypeptide, cells for expressing and/or producing the stabilized DNase I polypeptide, and methods of use of the stabilized DNase I polypeptide.