Combinatorial Generation of Chemical Diversity by Redox Enzymes in Chaetoviridin Biosynthesis

Org Lett. 2016 Mar 18;18(6):1446-9. doi: 10.1021/acs.orglett.6b00380. Epub 2016 Mar 9.

Abstract

Chaetoviridins constitute a large family of structurally related secondary metabolites isolated from Chaetomium fungi. To elucidate the biosynthesis pathway and understand how the chemical diversity of chaetoviridins is generated, gene deletion and in vitro characterization of the four post-PKS modifications enzymes were undertaken. CazL and CazP were identified to have substrate promiscuity that facilitates the formation of nonchlorinated analogues. In addition, enzymatic oxidation and reduction combined with spontaneous dehydration and lactonization of the intermediates further expand the chemical diversity.

Publication types

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

MeSH terms

  • Biosynthetic Pathways
  • Chaetomium / chemistry*
  • Furans / chemistry
  • Furans / metabolism*
  • Gene Deletion
  • Molecular Structure
  • Oxidation-Reduction
  • Polyketide Synthases / metabolism*
  • Pyrones / chemistry
  • Pyrones / metabolism*

Substances

  • Furans
  • Pyrones
  • chaetoviridin A
  • Polyketide Synthases