Enzymes are efficient nanomachines which have usually evolved for some specific functions. Therefore, tweaking enzymes for functional versatility, and harnessing their catalytic efficiency for commercial applications, has become a holy grail for bioengineers. Due to the versatility in functions and the capability of activating the C-H bond which is a commercially important process, Cytochrome P450 (CYP450) provides an ideal scaffold for bioengineering through directed evolution. The native CYP450 uses molecular oxygen and attaches one oxygen to the substrate while the second oxygen is reduced as a water molecule. An axial thiolate ligand (Cysteine) that controls the electron density via the push-pull effect is the hallmark residue of all CYP450 enzymes. Among the members of the P450 family, CYP450BM3 possesses the widest and most exposed substrate-access channel, and exhibits as such the highest degree of promiscuity among CYP450s. As such, CYP450BM3 has been widely used as a scaffold for bioengineering of nonnative reactions such as Carbene-and Nitrene-transfer reactions. Generally, the naturally occurring CYP450s perform C-H activation through monooxygenation but none of the natural enzymes exhibits in its repertoire C-H bond amination.