title: Remarkably different structures and reaction mechanisms of ketoreductases for the opposite stereochemical control in the biosynthesis of BIQ antibiotics.
abstract: Two ketoreductases, RED1 and RED2, are involved in the biosynthesis of actinorhodin in Streptomyces coelicolor A3(2) and dihydrogranaticin in S. violaceoruber 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Taguchi
authors.forename: Kanako
authors.initials: K
authors.lastname: Kunieda
authors.forename: Mayuko
authors.initials: M
authors.lastname: Takeda-Shitaka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takaya
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kawano
authors.forename: Meriel R
authors.initials: MR
authors.lastname: Kimberley
authors.forename: Kevin I
authors.initials: KI
authors.lastname: Booker-Milburn
authors.forename: G Richard
authors.initials: GR
authors.lastname: Stephenson
authors.forename: Hideaki
authors.initials: H
authors.lastname: Umeyama
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ebizuka
authors.forename: Koji
authors.initials: K
authors.lastname: Ichinose
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011809:Quinones / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D011809:Quinones; D000429:Alcohol Oxidoreductases