Highly Selective Indole Oxidation Catalyzed by a Mn-Containing Artificial Mini-Enzyme

Abstract

Indole oxidation represents a real challenge for selectivity because it typically leads to complex mixtures of products even when highly selective enzymes are used. Here, we describe the catalytic potential of an artificial enzyme, Mn-Mimochrome VI*a (Mn-MC6*a), in promoting indole oxidation. This mini-enzyme contains a manganese−deuteroporphyrin active site within a scaffold of two synthetic small peptides covalently linked to porphyrin. Mn-MC6*a promotes the selective oxidation of indole at its C3 position, leading to a 3-oxindole derivative (2-TFE-3oxindole) with unprecedented product selectivity (86% at pH 8.5) compared to native or artificial heme-enzymes. We also suggest a possible reaction mechanism based on the effect of pH, cosolvent, and indole substitution on the reaction outcome. These studies demonstrate that Mn-MC6*a is an excellent artificial peroxygenase for the production of 3-oxindole-containing compounds as key building blocks for the synthesis of fine chemicals.

Design and Engineering of an Efficient Peroxidase Using Myoglobin for Dye Decolorization and Lignin Bioconversion

“…It should be noted that although the contribution of R67 in k cat could hardly be deduced between the quadruple and triple mutant, its role was indicated by the comparison of F43Y Mb and F43Y/T67R Mb ( Table 1 ). Moreover, a distal Arg was demonstrated to be essential for regulating the structure and reactivity of artificial heme enzymes [ 36 , 37 ].…”

Transition Metal Scaffolds Used To Bring New‐to‐Nature Reactions into Biological Systems

“…[144][145][146][147] For instance, mimochromes are an enzyme class specifically designed so that two short peptide chains are covalently bound to a metaldeuteroporphyrin complex, thereby simulating a helix-hemehelix sandwiched structure typically found in nature. [144][145][146] A good example of its usage can be seen with manganese-based mimochromes, where selective C3 oxidation of indole was shown to proceed with excellent product selectivity compared to controls. [145] In terms of protein-based scaffolds, it would be nearly impossible to overlook the influence that streptavidin/avidin has had since the Whiteside group first introduced an avidin ArM in 1978.…”

“…[144][145][146] A good example of its usage can be seen with manganese-based mimochromes, where selective C3 oxidation of indole was shown to proceed with excellent product selectivity compared to controls. [145] In terms of protein-based scaffolds, it would be nearly impossible to overlook the influence that streptavidin/avidin has had since the Whiteside group first introduced an avidin ArM in 1978. [148] The main advantage of avidin/streptavidin are their strong affinities to the small molecule biotin, which can be used to easily anchor different metal complexes to catalyze various transformations.…”

“…Despite limited cases, one of the most basic scaffolds for metal coordination has been small peptides [144–147] . For instance, mimochromes are an enzyme class specifically designed so that two short peptide chains are covalently bound to a metal‐deuteroporphyrin complex, thereby simulating a helix‐heme‐helix sandwiched structure typically found in nature [144–146] .…”

“…Despite limited cases, one of the most basic scaffolds for metal coordination has been small peptides. [144][145][146][147] For instance, mimochromes are an enzyme class specifically designed so that two short peptide chains are covalently bound to a metaldeuteroporphyrin complex, thereby simulating a helix-hemehelix sandwiched structure typically found in nature. [144][145][146] A good example of its usage can be seen with manganese-based mimochromes, where selective C3 oxidation of indole was shown to proceed with excellent product selectivity compared to controls.…”