A Polyketide Cyclase That Forms Medium-Ring Lactones

J Am Chem Soc. 2021 Jan 13;143(1):80-84. doi: 10.1021/jacs.0c11226. Epub 2020 Dec 22.

Abstract

Medium-ring lactones are synthetically challenging due to unfavorable energetics involved in cyclization. We have discovered a thioesterase enzyme DcsB, from the decarestrictine C1 (1) biosynthetic pathway, that efficiently performs medium-ring lactonizations. DcsB shows broad substrate promiscuity toward linear substrates that vary in lengths and substituents, and is a potential biocatalyst for lactonization. X-ray crystal structure and computational analyses provide insights into the molecular basis of catalysis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Beauveria / enzymology
  • Beauveria / genetics
  • Biocatalysis
  • Crystallography, X-Ray
  • Cyclization
  • Esterification
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Lactones / chemical synthesis*
  • Lactones / metabolism
  • Molecular Docking Simulation
  • Multigene Family
  • Protein Binding
  • Substrate Specificity
  • Thiolester Hydrolases / chemistry*
  • Thiolester Hydrolases / genetics
  • Thiolester Hydrolases / metabolism

Substances

  • Fungal Proteins
  • Lactones
  • Thiolester Hydrolases