Remarkably different structures and reaction mechanisms of ketoreductases for the opposite stereochemical control in the biosynthesis of BIQ antibiotics.
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.
Taguchi
Takaaki
T
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kunieda
Kanako
K
Takeda-Shitaka
Mayuko
M
Takaya
Daisuke
D
Kawano
Noriaki
N
Kimberley
Meriel R
MR
Booker-Milburn
Kevin I
KI
Stephenson
G Richard
GR
Umeyama
Hideaki
H
Ebizuka
Yutaka
Y
Ichinose
Koji
K
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
D000900:Anti-Bacterial Agents; D011809:Quinones; D000429:Alcohol Oxidoreductases