A Heme–Peptide Metalloenzyme Mimetic with Natural Peroxidase-Like Activity

Mimicking enzymes with alternative molecules represents an important objective in synthetic biology, aimed to obtain new chemical entities for specific applications. This objective is hampered by the large size and complexity of enzymes. The manipulation of their structures often leads to a reduction of enzyme activity. Here, we describe the spectroscopic and functional characterization of FeIII-Mimochrome VI, a 3.5 kDa synthetic heme-protein model, which displays a peroxidase-like catalytic activity. By the use of hydrogen peroxide, it efficiently catalyzes the oxidation of several substrates, with a typical Michaelis-Menten mechanism and with several multiple turnovers. The catalytic efficiency of FeIII-Mimochrome VI in the oxidation of ABTS and guaiacol (kcat/Km = 4417 and 870 mM-1 s-1, respectively) is comparable to that of native HRP (kcat/Km = 5125 and 500 mM-1 s-1, respectively). FeIII-Mimochrome VI also converts phenol to 4- and 2-nitrophenol in the presence of NO2- and H2O2 in high yields. These results demonstrate that small synthetic peptide can impart high enzyme activities to metal cofactors, and anticipate the possibility of constructing new biocatalysts tailored to specific functions.