Mn-Mimochrome VI*a: An Artificial Metalloenzyme With Peroxygenase Activity

Abstract

Manganese-porphyrins are important tools in catalysis, due to their capability to promote a wide variety of synthetically valuable transformations. Despite their great reactivity, the difficulties to control the reaction selectivity and to protect the catalyst from self-degradation hamper their practical application. Compared to small-molecule porphyrin complexes, metalloenzymes display remarkable features, because the reactivity of the metal center is finely modulated by a complex interplay of interactions within the protein matrix. In the effort to combine the catalytic potential of manganese porphyrins with the unique properties of biological catalysts, artificial metalloenzymes have been reported, mainly by incorporation of manganese-porphyrins into native protein scaffolds. Here we describe the spectroscopic and catalytic properties of Mn-Mimochrome VI*a (Mn-MC6*a), a mini-protein with a manganese deuteroporphyrin active site within a scaffold of two synthetic peptides covalently bound to the porphyrin. Mn-MC6*a is an efficient catalyst endowed with peroxygenase activity. The UV-vis absorption spectrum of Mn-MC6*a resembles that of Mn-reconstituted horseradish peroxidase (Mn-HRP), both in the resting and high-valent oxidized states. Remarkably, Mn-MC6*a shows a higher reactivity compared to Mn-HRP, because higher yields and chemoselectivity were observed in thioether oxidation. Experimental evidences also provided indications on the nature of the high-valent reactive intermediate and on the sulfoxidation mechanism.

Mimochrome, a metalloporphyrin‐based catalytic Swiss knife†

“…MnMC6*a, as well as its iron congener, was screened for peroxygenase-like catalysis, using the H 2 O 2 -mediated thioether sulfoxidation as test reaction. Both FeMC6*a and MnMC6*a complexes demonstrated to efficiently promote the selective conversion of phenyl thioethers into the corresponding sulfoxides, with experimental evidences of a direct oxygen-transfer mechanism [286]. Thioether oxidation by Mn-and FeMC6*a shows a pHdependency that closely resembles that of peroxide activation, thereby suggesting the involvement of the ferryl or manganyloxo species in the reaction.…”

Clickable artificial heme‐peroxidases for the development of functional nanomaterials

“…Along these lines, we have developed artificial metalcontaining biocatalysts, named mimochromes (MCs), by using a miniaturization process on hemeproteins [1,11,12,[25][26][27][28][29][30][31][32][33][34]. MCs consist of a helix-heme-helix sandwich, made up by two small peptide chains covalently linked to deuteroporphyrin.…”

“…This simple modification rendered MC6*a the most proficient and stable scaffold for modulating the reactivity of the porphyrin metal ion. MC6*a iron and manganese complexes were found to be competent catalysts in peroxidase and peroxygenase activities [31,32], respectively, whereas the cobalt derivative was active in hydrogen evolution catalysis [33,34].…”

Exploring and Adapting the Molecular Selectivity of Artificial Metalloenzymes

“…With the 3-D structural support of these systems, asymmetric reactions have been shown to proceed for a number of epoxidation, [164][165][166][167] hydroxylation, [168][169] and oxidation reactions. 164,[170][171][172] Furthermore, the dismutation activity of a number of ArMs also opens the door for their application as superoxide dismutase (SOD) mimics. 166,173 Given the lack of literature examples, our group has begun to explore the early frameworks of gold-based ArMs.…”