Molecular mechanisms of enzyme-catalysed halogenation

J. L. Ross Anderson, Stephen K. Chapman*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

31 Citations (Scopus)

Abstract

Since their discovery, halogenated metabolites have been somewhat of a biological peculiarity and it is only now that we are beginning to realize the full extent of their medicinal value. With the exception of the well characterized haloperoxidases, most of the biosynthetic enzymes and mechanisms responsible for the halogenations have remained elusive. The crystal structures of two functionally diverse halogenases have been recently solved, providing us with new and exciting mechanistic detail. This new insight has the potential to be used both in the development of biomimetic halogenation catalysts and in engineering halogenases, and related enzymes, to halogenate new substrates. Interestingly, these new structures also illustrate how the evolution of these enzymes mirrors that of the monooxygenases, where the cofactor is selected for its ability to generate a powerful oxygenating species. In this highlight article we will examine the proposed catalytic mechanisms of the halogenases and how these relate to their structures. In addition, we will consider how this chemistry might be harnessed and developed to produce novel enzymatic activity.

Original languageEnglish
Pages (from-to)350-357
Number of pages8
JournalMolecular bioSystems
Volume2
Issue number8
DOIs
Publication statusPublished - Aug 2006

Keywords

  • BIOSYNTHETIC GENE-CLUSTER
  • OCCURRING ORGANOHALOGEN COMPOUNDS
  • TRYPTOPHAN 7-HALOGENASE PRNA
  • VANILLYL-ALCOHOL OXIDASE
  • PSEUDOMONAS-FLUORESCENS
  • CRYSTAL-STRUCTURE
  • ACTIVE-SITE
  • CHLORINATION
  • PYRROLNITRIN
  • REBECCAMYCIN

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