Biosynthesis of salinosporamides from alpha,beta-unsaturated fatty acids: implications for extending polyketide synthase diversity

J Am Chem Soc. 2009 Aug 5;131(30):10376-7. doi: 10.1021/ja9042824.

Abstract

A new series of coenzyme A-tethered polyketide synthase extender units were discovered in relation to the biosynthesis of the salinosporamide family of anticancer agents from the marine bacterium Salinispora tropica. In vivo and in vitro experiments revealed that the crotonyl-CoA reductase/carboxylase SalG has broad substrate tolerance toward 2-alkenyl-CoAs that give rise to the salinosporamide C-2 substitution pattern.

Publication types

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

MeSH terms

  • Actinomycetales / metabolism
  • Acyl Coenzyme A / metabolism
  • Chromatography, High Pressure Liquid
  • Fatty Acids, Unsaturated / metabolism*
  • Lactams / chemistry
  • Lactams / metabolism*
  • Polyketide Synthases / metabolism*

Substances

  • Acyl Coenzyme A
  • Fatty Acids, Unsaturated
  • Lactams
  • methylmalonyl-coenzyme A
  • Polyketide Synthases