In vitro precursor-directed synthesis of polyketide analogues with coenzyme a regeneration for the development of antiangiogenic agents

Org Lett. 2009 Sep 3;11(17):3806-9. doi: 10.1021/ol901243e.

Abstract

Polyketide analogues are produced via in vitro reconstruction of a precursor-directed polyketide biosynthetic pathway. Malonyl-CoA synthetase (MCS) was used in conjunction with chalcone synthase (CHS), thereby allowing efficient use of synthetic starter molecules and malonate as extender. Coenzyme-A was recycled up to 50 times. The use of a simple immobilization procedure resulted in up to a 30-fold higher yield of pyrone CHS products than that obtained with the free enzyme solutions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / metabolism*
  • Adenosine Triphosphate / chemistry
  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Bacterial Proteins / metabolism*
  • Biological Products / chemical synthesis*
  • Biological Products / chemistry
  • Catalysis
  • Coenzyme A / metabolism*
  • Coenzyme A Ligases / metabolism*
  • Macrolides / chemical synthesis*
  • Macrolides / chemistry
  • Molecular Structure
  • Pyrones

Substances

  • Angiogenesis Inhibitors
  • Bacterial Proteins
  • Biological Products
  • Macrolides
  • Pyrones
  • Adenosine Triphosphate
  • Acyltransferases
  • flavanone synthetase
  • Coenzyme A Ligases
  • malonyl-CoA synthetase
  • Coenzyme A