In vitro reconstruction of tetronate RK-682 biosynthesis

Nat Chem Biol. 2010 Feb;6(2):99-101. doi: 10.1038/nchembio.285. Epub 2009 Dec 20.

Abstract

The protein phosphatase inhibitor RK-682 is one of a number of potentially valuable tetronate polyketide natural products. Understanding how the tetronate ring is formed has been frustrated by the inaccessibility of the putative substrates. We report the heterologous expression of rk genes in Saccharopolyspora erythraea and reconstitution of the RK-682 pathway using recombinant enzymes, and we show that RkD is the enzyme required for RK-682 formation from acyl carrier protein-bound substrates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism*
  • Molecular Structure
  • Multigene Family
  • Phosphoprotein Phosphatases / antagonists & inhibitors*
  • Phosphoprotein Phosphatases / biosynthesis
  • Phosphoprotein Phosphatases / chemistry
  • Saccharopolyspora / chemistry
  • Saccharopolyspora / genetics
  • Saccharopolyspora / metabolism*
  • Substrate Specificity

Substances

  • Bacterial Proteins
  • Enzyme Inhibitors
  • RK 682
  • Phosphoprotein Phosphatases