The thioesterase domain from the pimaricin and erythromycin biosynthetic pathways can catalyze hydrolysis of simple thioester substrates

Bioorg Med Chem Lett. 2007 Jun 1;17(11):3034-7. doi: 10.1016/j.bmcl.2007.03.060. Epub 2007 Mar 23.

Abstract

The recombinant polyketide synthase thioesterase domains from the pimaricin and 6-deoxyerythronolide B biosynthetic pathways catalyze hydrolysis of a number of simple N-acetylcysteamine thioester derivatives. This study demonstrates that thioesterases are not highly substrate selective in formation of the acyl-enzyme intermediate, in contrast to non-ribosomal peptide synthase thioesterase domains that show very high specificity for substrate loading. This observation has important implications for the engineering of biosynthetic pathways to produce polyketide products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosynthetic Pathways
  • Catalysis
  • Cysteamine / analogs & derivatives*
  • Erythromycin / analogs & derivatives
  • Erythromycin / biosynthesis*
  • Esters / chemistry
  • Hydrolysis
  • Natamycin / biosynthesis*
  • Polyketide Synthases / chemistry*
  • Polyketide Synthases / genetics
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Substrate Specificity
  • Sulfur Compounds / chemistry*
  • Thiolester Hydrolases / chemistry*
  • Thiolester Hydrolases / genetics

Substances

  • Esters
  • Recombinant Proteins
  • Sulfur Compounds
  • 6-deoxyerythronolide B
  • Cysteamine
  • Erythromycin
  • Polyketide Synthases
  • Natamycin
  • Thiolester Hydrolases