Development of myoglobin-based catalyst for reactions with organic radicals Andriy Lubskyy 1 , Fink Alke 1 , Bruns Nico 2 and Pellizzoni Michela 1 1 Adolphe Merkle Institute, Switzerland, 2 Department of Chemistry, Technical University of Darmstadt, Germany Enzymes can perform clean chemo-, regio- and stereoselective transformations very efficiently under mild physiological conditions, however the scope of this reactions is limited by those essential for life. Adaptation of existing enzymes for the catalysis of reactions not previously observed in nature is one of the way to use the enzymes for human needs. 1 Since some porphyrine-based proteins 2 and catalysts 3 can perform Atom Transfer Radical Polymerisations (ATRP), we hypothesised that heme-containing proteins can catalyse organic radical based reactions with small molecules, such as Atom Transfer Radical Cyclisation (ATRC). Out of the range of heme containing proteins we selected myoglobin due to its well characterised structure, stability to mutagenesis and availability other engineering modes, like cofactor substitution. 4, 5 After introducting mutations targeting amino acids in the iron- heme coordination sphere, and therefore adjusting the pocket dimensions, polarity and metal redox properties, we were able to introduce and modulate non-natural ATRC activity in purified proteins and whole cells expressing modified myoglobin, thus paving a way to introduce new-to-nature radical reactivity into industrial biocatalytic pathways and microbial metabolism. References 1. Brandenberg, O. F.; Fasan, R.; Arnold, F. H. Curr. Opin. Biotechnol. 2017, 47, 102. 2. Rodriguez, K. J.; Gajewska, B.; Pollard, J.; Pellizzoni, M. M.; Fodor, C.; Bruns, N. Acs Macro Letters 2018, 7 (9), 1111. 3. Simakova, A.; Mackenzie, M.; Averick, S. E.; Park, S.; Matyjaszewski, K. Angew. Chem. Int. Ed. Engl. 2013, 52 (46), 12148. 4. Key, H. M.; Dydio, P.; Clark, D. S.; Hartwig, J. F. Nature 2016, 534 (7608), 534. 5. Vargas, D. A.; Khade, R. L.; Zhang, Y.; Fasan, R. Angew. Chem. Int. Ed. Engl. 2019, 58 (30), 10148.
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