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- Title
Directed Evolution of RebH for Site-Selective Halogenation of Large Biologically Active Molecules.
- Authors
Payne, James T.; Poor, Catherine B.; Lewis, Jared C.
- Abstract
We recently characterized the substrate scope of wild-type RebH and proceeded to evolve variants of this enzyme with improved stability for biocatalysis. The substrate scopes of both RebH and the stabilized variants, however, are limited primarily to compounds similar in size to tryptophan. A substrate walking approach was used to further evolve RebH variants with expanded substrate scope. Two particularly notable variants were identified: 3-SS, which provides high conversion of tricyclic tryptoline derivatives; and 4-V, which accepts a broad range of large indoles and carbazoles. This constitutes the first reported use of directed evolution to enable the functionalization of substrates not accepted by wild-type RebH and demonstrates the utility of RebH variants for the site-selective halogenation of biologically active compounds.
- Subjects
HALOGENATION; ENZYMES; BIOCATALYSIS; TRYPTOPHAN; INDOLE compounds; CARBAZOLE; BIOCHEMICAL substrates
- Publication
Angewandte Chemie, 2015, Vol 127, Issue 14, p4300
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201411901