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Development of halogenase enzymes for use in synthesis
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Latham, Jonathan, Brandenburger, Eileen, Shepherd, Sarah A., Menon, Binuraj R. K. and Micklefield, Jason (2017) Development of halogenase enzymes for use in synthesis. Chemical Reviews . doi:10.1021/acs.chemrev.7b00032
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Official URL: http://dx.doi.org/10.1021/acs.chemrev.7b00032
Abstract
Nature has evolved halogenase enzymes to regioselectively halogenate a diverse range of biosynthetic precursors, with the halogens introduced often having a profound effect on the biological activity of the resulting natural products. Synthetic endeavors to create non-natural bioactive small molecules for pharmaceutical and agrochemical applications have also arrived at a similar conclusion: halogens can dramatically improve the properties of organic molecules for selective modulation of biological targets in vivo. Consequently, a high proportion of pharmaceuticals and agrochemicals on the market today possess halogens. Halogenated organic compounds are also common intermediates in synthesis and are particularly valuable in metal-catalyzed cross-coupling reactions. Despite the potential utility of organohalogens, traditional nonenzymatic halogenation chemistry utilizes deleterious reagents and often lacks regiocontrol. Reliable, facile, and cleaner methods for the regioselective halogenation of organic compounds are therefore essential in the development of economical and environmentally friendly industrial processes. A potential avenue toward such methods is the use of halogenase enzymes, responsible for the biosynthesis of halogenated natural products, as biocatalysts. This Review will discuss advances in developing halogenases for biocatalysis, potential untapped sources of such biocatalysts and how further optimization of these enzymes is required to achieve the goal of industrial scale biohalogenation.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||
| Journal or Publication Title: | Chemical Reviews | ||||
| Publisher: | American Chemical Society | ||||
| ISSN: | 0009-2665 | ||||
| Official Date: | 3 May 2017 | ||||
| Dates: |
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| DOI: | 10.1021/acs.chemrev.7b00032 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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