Inspired by this mechanistic insight, we set out to explore the possibility of engineering an artificial peroxidase with enhanced rates and improved efficiency by embedding a Feporphyrin (FePP) cofactor into a protein environment. In a biomimetic spirit, this approach provides a well-defined second coordination sphere around the cofactor, which can be optimized via genetic means. To achieve this, we selected streptavidin (Sav) as protein scaffold. On one hand, Sav is stable under chaotropic conditions such as high temperatures, pH extremes (1 < pH < 13), and in the presence of organic co-solvents. On the other hand, the remarkable affinity of biotin (Biot) for Sav (Ka > 10 10 M -1 ) provides an attractive means to anchor (nearly) any biotinylated probe within Sav. Herein, we report on our efforts to design and evolve an artificial peroxidase with best-in-class catalytic efficiency based on anchoring a bis-biotinylated Fe-porphyrin within streptavidin.