Logically, this Histidine residue should be a plausible proton donor that enables the formation of Cpd I from H2O2. 17b This is further supported by the fact that a Q85H (Q is Glutamine (Gln)) mutation in P450BSβ increases the decarboxylation activity over hydroxylation in the so-mutated P450BSβ. Suggestions that the substrate identity is somehow involved in changing the mechanism were ruled out by As such, the primary mechanistic puzzle which is targeted here, is: how does the presence or absence of H85 diversify the decarboxylation and hydroxylation activities in the WT P450BSβ and WT P450OleT P450 enzymes? These issues are addressed herein by means of a combination of MD simulations and QM/MM studies of the P450OleT and P450BSβ enzymes. As shall be seen, the study uncovers the nimble ability of evolution to bioengineer reactions using a mutation of a single protein residue, which affects its local electric field (LEF) and hence its function.