By leveraging the Biotin-Sav technology, we have designed, engineered, and genetically-optimized an artificial peroxidase that efficiently oxidizes organic substrates. Our design incorporates a ligand with a polar amino acid spacer between the biotin anchor and FePP moiety, which ensures the formation of discrete Biot2-FePP • Sav assemblies instead of cross-linked Sav aggregates. This was confirmed through HRMS and X-ray crystallography. The cofactor alone has activity for substrate oxidation, but its rate and efficiency are significantly improved upon anchoring in Sav. Through genetic optimization, we further improved the catalytic activity of this artificial peroxidase. To the best of our knowledge, the catalytic efficiency of the genetically-engineered artificial peroxidase exceeds that of all peroxidases reported to date. Moving forward, we aim to explore this work by evaluating a large library of Sav isoforms, including chimeric streptavidin with a shielded