Menon, Binuraj R. K., Brandenburger, Eileen, Sharif, Humera H., Klemstein, Ulrike, Shepherd, Sarah A., Greaney, Michael F. and Micklefield, Jason (2017) RadH : a versatile halogenase for integration into synthetic pathways. Angewandte Chemie International Edition, 56 (39). pp. 11841-11845. doi:10.1002/anie.201706342

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Abstract

Flavin-dependent halogenases are useful enzymes for providing halogenated molecules with improved biological activity, or intermediates for synthetic derivatization. We demonstrate how the fungal halogenase RadH can be used to regioselectively halogenate a range of bioactive aromatic scaffolds. Site-directed mutagenesis of RadH was used to identify catalytic residues and provide insight into the mechanism of fungal halogenases. A high-throughput fluorescence screen was also developed, which enabled a RadH mutant to be evolved with improved properties. Finally we demonstrate how biosynthetic genes from fungi, bacteria, and plants can be combined to encode a new pathway to generate a novel chlorinated coumarin “non-natural” product in E. coli.

Item Type:	Journal Article
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Journal or Publication Title:	Angewandte Chemie International Edition
Publisher:	Wiley - V C H Verlag GmbH & Co. KGaA
ISSN:	1433-7851
Official Date:	18 September 2017
Dates:	Date Event 18 September 2017 Published 19 August 2017 Accepted
Volume:	56
Number:	39
Page Range:	pp. 11841-11845
DOI:	10.1002/anie.201706342
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access

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