A thioesterase from an iterative fungal polyketide synthase shows macrocyclization and cross coupling activity and may play a role in controlling iterative cycling through product offloading

Biochemistry. 2009 Jul 14;48(27):6288-90. doi: 10.1021/bi9009049.

Abstract

Zearalenone, a fungal macrocyclic polyketide, is a member of the resorcylic acid lactone family. Herein, we characterize in vitro the thioesterase from PKS13 in zearalenone biosynthesis (Zea TE). The excised Zea TE catalyzes macrocyclization of a linear thioester-activated model of zearalenone. Zea TE also catalyzes the cross coupling of a benzoyl thioester with alcohols and amines. Kinetic characterization of the cross coupling is consistent with a ping-pong bi-bi mechanism, confirming an acyl-enzyme intermediate. Finally, the substrate specificity of the Zea TE indicates the TE may help control iterative cycling on PKS13 by rapidly offloading the final resorcylate-containing product.

Publication types

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

MeSH terms

  • Biocatalysis
  • Chromatography, High Pressure Liquid
  • Cyclization
  • Esterases / metabolism*
  • Gibberella / enzymology*
  • Kinetics
  • Polyketide Synthases / chemistry
  • Polyketide Synthases / metabolism*
  • Substrate Specificity

Substances

  • Polyketide Synthases
  • Esterases