A Structure-Guided Switch in the Regioselectivity of a Tryptophan Halogenase

Research output: Research - peer-reviewArticle

  • External authors:
  • Sarah Shepherd
  • Binuraj Menon
  • Heidi Fisk
  • Anna-Winona Struck


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.

Bibliographical metadata

Original languageEnglish
Pages (from-to)821–824
JournalChemBioChem: a European journal of chemical biology
Early online date30 Mar 2016
StatePublished - 3 May 2016