Exploring the Biocatalytic Potential of Fe/α-Ketoglutarate-Dependent Halogenases
- 10 June 2020
- journal article
- research article
- Published by Wiley in Chemistry – A European Journal
- Vol. 26 (33), 7336-7345
- https://doi.org/10.1002/chem.201905752
Abstract
Freestanding Fe/alpha-ketoglutarate-dependent halogenases are oxidoreductases that catalyze the installation of halogen atoms into unactivated sp(3)-hybridized carbon centers with high stereo- and regioselectivity. Since their discovery in 2014, a small number of indole alkaloid and amino acid halogenases have been identified and characterized. First enzyme engineering examples suggest that the accessible substrate range of these enzymes may be expanded through the use of rational enzyme design and directed evolution. Structural investigations of non-heme iron halogenases acting on freestanding as well as tethered substrates are beginning to inform about the principles of the underlying halogenation mechanism.Funding Information
- Staatssekretariat für Bildung, Forschung und Innovation (Federal project contributions 2017-2020, P-14: Innovation in Biocatalysis)
This publication has 115 references indexed in Scilit:
- Integrating carbon–halogen bond formation into medicinal plant metabolismNature, 2010
- Conformational switch triggered by α-ketoglutarate in a halogenase of curacin A biosynthesisProceedings of the National Academy of Sciences of the United States of America, 2010
- Chloramphenicol Biosynthesis: The Structure of CmIS, a Flavin-Dependent Halogenase Showing a Covalent Flavin-Aspartate BondJournal of Molecular Biology, 2010
- Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-HydroxylasePLOS ONE, 2009
- Substrate positioning controls the partition between halogenation and hydroxylation in the aliphatic halogenase, SyrB2Proceedings of the National Academy of Sciences of the United States of America, 2009
- Structural Insights into Regioselectivity in the Enzymatic Chlorination of TryptophanJournal of Molecular Biology, 2009
- Structural Analysis of an Open Active Site Conformation of Nonheme Iron Halogenase CytC3Journal of the American Chemical Society, 2009
- New Insights into the Mechanism of Enzymatic Chlorination of TryptophanAngewandte Chemie, 2008
- Discovery and characterization of a marine bacterial SAM-dependent chlorinaseNature Chemical Biology, 2007
- Enantioselective α-Hydroxylation of 2-Arylacetic Acid Derivatives and Buspirone Catalyzed by Engineered Cytochrome P450 BM-3Journal of the American Chemical Society, 2006