5hy5

Publication Abstract from PubMed

Flavin-dependent halogenase enzymes are potentially useful biocatalysts for the regioselectively halogenation of aromatic compounds. Haloaromatic compounds can be utilised in the synthesis and biosynthesis of pharmaceuticals and other valuable products. Here we report the first X-ray crystal structure of a tryptophan 6-halogenase (SttH), which enabled key residues that contribute to the regioselectivity in tryptophan halogenases to be identified. Structure-guided mutagenesis resulted in a triple mutant (L460F/P461E/P462T) that exhibited a complete switch in regioselectivity; with the substrate 3-indolepropionate 75% 5-chlorination was observed with the mutant in comparison with 90% 6-chlorination for the wild-type SttH. This is the first clear example of how regiocomplementary halogenase enzymes can be created from a single parent enzyme. The biocatalytic repertoire of SttH was also expanded to include a range of indolic and non-indolic substrates.

A Structure-Guided Switch in the Regioselectivity of a Tryptophan Halogenase Enzyme.,Shepherd SA, Menon BR, Fisk H, Struck AW, Levy C, Leys D, Micklefield J Chembiochem. 2016 Feb 3. doi: 10.1002/cbic.201600051. PMID:26840773^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.