Further Characterization of Fungal Halogenase RadH and Its Homologs

GuangRong Peh, Gregory A. Gunawan, Terence Tay, Elaine Tiong, Lee Ling Tan, Shimin Jiang, Yi Ling Goh, Suming Ye, Joel Wong, Christopher J. Brown, Huimin Zhao, Ee Lui Ang, Fong Tian Wong, Yee Hwee Lim

Research output: Contribution to journalArticlepeer-review

Abstract

RadH is one of the flavin-dependent halogenases that has previously exhibited promising catalytic activity towards hydroxycoumarin, hydroxyisoquinoline, and phenolic derivatives. Here, we evaluated new functional homologs of RadH and expanded its specificities for the halogenation of non-tryptophan-derived, heterocyclic scaffolds. Our investigation revealed that RadH could effectively halogenate hydroxyquinoline and hydroxybenzothiophene. Assay optimization studies revealed the need to balance the various co-factor concentrations and where a GDHi co-factor recycling system most significantly improves the conversion and efficiency of the reaction. A crystal structure of RadH was also obtained with a resolution of 2.4 Å, and docking studies were conducted to pinpoint the binding and catalytic sites for substrates.
Original languageEnglish (US)
Article number1081
JournalBiomolecules
Volume13
Issue number7
DOIs
StatePublished - Jul 2023

Keywords

  • X-ray crystallography
  • heteroaromatic
  • halogenation
  • flavin-dependent halogenases

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

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