Remarkably different structures and reaction mechanisms of ketoreductases for the opposite stereochemical control in the biosynthesis of BIQ antibiotics

Takaaki Taguchi, Kanako Kunieda, Mayuko Takeda-Shitaka, Daisuke Takaya, Noriaki Kawano, Meriel R. Kimberley, Kevin I. Booker-Milburn, G. Richard Stephenson, Hideaki Umeyama, Yutaka Ebizuka, Koji Ichinose

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

15 Citations (Scopus)

Abstract

Remarkably different reduction mechanisms and structures of two stereospecific ketoreductases, RED1 and RED2, giving the opposite enantiomeric intermediates in the BIQ biosyntheses: new insights obtained by biochemical experiments and bioinformatics. Two ketoreductases, RED1 and RED2, are involved in the biosynthesis of actinorhodin in Streptomyces coelicolor A3(2) and dihydrogranaticin in S. violaceoruber Tü22, respectively. They are responsible for the stereospecific reductions of the bicyclic intermediate to give (S)- or (R)-DNPA, although there is no similarity between their amino acid sequences. Biotransformation using synthetic analogous substrates revealed that the substrate specificities are quite different. Homology modelling studies and site directed mutagenesis showed remarkable differences in three-dimensional structures and catalytic mechanisms between RED1 and RED2. © 2004 Elsevier Ltd. All rights reserved.

Translated title of the contributionRemarkably different structures and reaction mechanisms of Ketoreductases for the opposite stereochemical control in the Biosynthesis of BIQ Antibiotics
Original languageEnglish
Pages (from-to)5917-5927
Number of pages11
JournalBioorganic and Medicinal Chemistry Letters
Volume12
Issue number22
DOIs
Publication statusPublished - 15 Nov 2004

Bibliographical note

Publisher: Pergamon Elsevier Sci. Ltd

Keywords

  • Benzoisochromanequinone antibiotics
  • Biotransformation
  • Homology modelling
  • Site directed mutagenesis
  • Stereospecific ketoreductase

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