Extending the biocatalytic scope of regiocomplementary flavin-dependent halogenase enzymes

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

doi:10.1039/c5sc00913h

Extending the biocatalytic scope of regiocomplementary flavin-dependent halogenase enzymes

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^*

^*Corresponding author for this work

University of Manchester

Research output: Contribution to journal › Article › peer-review

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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. This journal is

Original language	English
Pages (from-to)	3454-3460
Number of pages	7
Journal	Chemical Science
Volume	6
Issue number	6
Early online date	10 Apr 2015
DOIs	https://doi.org/10.1039/c5sc00913h
Publication status	Published - 1 Jun 2015

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title = "Extending the biocatalytic scope of regiocomplementary flavin-dependent halogenase enzymes",

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. This journal is",

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AU - Shepherd, Sarah A.

AU - Karthikeyan, Chinnan

AU - Latham, Jonathan

AU - Struck, Anna Winona

AU - Thompson, Mark L.

AU - Menon, Binuraj R. K.

AU - Styles, Matthew Q.

AU - Levy, Colin

AU - Leys, David

AU - Micklefield, Jason

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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. This journal is

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Extending the biocatalytic scope of regiocomplementary flavin-dependent halogenase enzymes

Abstract

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