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

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15 Citations (Scopus)

Abstract

Two ketoreductases, RED1 and RED2, are involved in the biosynthesis of actinorhodin in Streptomyces coelicolor A3(2) and dihydrogranaticin in S. violaceoruher Tu22 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. (C) 2004 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)5917-5927
Number of pages11
JournalBioorganic & Medicinal Chemistry
Volume12
Issue number22
DOIs
Publication statusPublished - 2004

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