Engineered biosynthesis of antiprotealide and other unnatural salinosporamide proteasome inhibitors

J Am Chem Soc. 2008 Jun 25;130(25):7822-3. doi: 10.1021/ja8029398. Epub 2008 May 31.

Abstract

A new shunt in the phenylalanine biosynthetic pathway to the nonproteinogenic amino acid L-3-cyclohex-2'-enylalanine was exploited in the marine bacterium Salinispora tropica by mutagenesis to allow for the genetic engineering of unnatural derivatives of the potent proteasome inhibitor salinosporamide A (2) such as antiprotealide (1).

Publication types

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

MeSH terms

  • Lactams / chemistry*
  • Lactams / metabolism*
  • Lactones / chemistry*
  • Lactones / metabolism*
  • Micromonosporaceae / genetics*
  • Molecular Structure
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / metabolism*
  • Proteasome Endopeptidase Complex / chemistry*
  • Protein Engineering*
  • Pyrroles / chemistry
  • Pyrroles / metabolism*

Substances

  • Lactams
  • Lactones
  • Protease Inhibitors
  • Pyrroles
  • antiprotealide
  • marizomib
  • Proteasome Endopeptidase Complex