Engineered biosynthesis of plant polyketides: manipulation of chalcone synthase

Org Lett. 2006 Feb 2;8(3):499-502. doi: 10.1021/ol052912h.

Abstract

[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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / chemistry*
  • Acyltransferases / metabolism
  • Binding Sites / physiology
  • Macrolides / chemical synthesis*
  • Macrolides / chemistry
  • Macrolides / metabolism
  • Molecular Conformation
  • Molecular Structure
  • Plants / chemistry*
  • Plants / enzymology*
  • Protein Biosynthesis
  • Scutellaria baicalensis / chemistry
  • Scutellaria baicalensis / genetics
  • Scutellaria baicalensis / metabolism*
  • Structure-Activity Relationship

Substances

  • Macrolides
  • Acyltransferases
  • flavanone synthetase