Engineered biosynthesis of plant polyketides: manipulation of chalcone synthase.
[reaction: see text]. Chalcone synthase (CHS) is a plant-specific type III polyketide synthase catalyzing condensation of 4-coumaroyl-CoA with three molecules of malonyl-CoA. Surprisingly, it was demonstrated that S338V mutant of Scutellaria baicalensis CHS produced octaketides SEK4/SEK4b from eight molecules of malonyl-CoA. Further, the octaketides-forming activity was dramatically increased in a CHS triple mutant (T197G/G256L/S338T). The functional conversion is based on the simple steric modulation of a chemically inert residue lining the active-site cavity.
Abe
Ikuro
I
School of Pharmaceutical Sciences and the COE 21 Program, University of Shizuoka, Shizuoka 422-8526, Japan. abei@ys7.u-shizuoka-ken.ac.jp
Watanabe
Tatsuya
T
Morita
Hiroyuki
H
Kohno
Toshiyuki
T
Noguchi
Hiroshi
H
D000217:Acyltransferases / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D015394:Molecular Structure; D010944:Plants / Q000737:chemistry* / Q000201:enzymology*; D014176:Protein Biosynthesis; D031364:Scutellaria baicalensis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D018942:Macrolides; D000217:Acyltransferases; C020141:flavanone synthetase