Extending the Biocatalytic Scope of Regiocomplementary Flavin-Dependent Halogenase Enzymes

Sarah Shepherd, Karthikeyan Chinnan Velmurugan, Jonathan Latham, Anna-Winona Struck, Mark Thompson, Binuraj Menon, Matthew Styles, Colin Levy, David Leys, Jason Micklefield

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)3454-3460
    JournalChemical Science
    Volume6
    DOIs
    Publication statusPublished - 2015

    Research Beacons, Institutes and Platforms

    • Manchester Institute of Biotechnology

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