Extending the biocatalytic scope of regiocomplementary flavin-dependent halogenase enzymes
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| Authors: | Sarah A. Shepherd Chinnan Karthikeyan Jonathan Latham Anna-Winona Struck Mark L. Thompson Binuraj R. K. Menon Matthew Q. Styles Colin Levy David Leys Jason Micklefield |
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| Affiliation: | a School of Chemistry , The University of Manchester , 131 Princess Street , Manchester , M1 7DN , UK . Email: ;b Manchester Institute of Biotechnology , The University of Manchester , 131 Princess Street , Manchester , M1 7DN , UK ;c Faculty of Life Sciences , The University of Manchester , 131 Princess Street , Manchester , M1 7DN , UK |
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| Abstract: | Flavin-dependent halogenases are potentially valuable biocatalysts for the regioselective halogenation of aromatic compounds. These enzymes, utilising benign inorganic halides, offer potential advantages over traditional non-enzymatic halogenation chemistry that often lacks regiocontrol and requires deleterious reagents. Here we extend the biocatalytic repertoire of the tryptophan halogenases, demonstrating how these enzymes can halogenate a range of alternative aryl substrates. Using structure guided mutagenesis we also show that it is possible to alter the regioselectivity as well as increase the activity of the halogenases with non-native substrates including anthranilic acid; an important intermediate in the synthesis and biosynthesis of pharmaceuticals and other valuable products. |
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