Comparison of 10,11-Dehydrocurvularin Polyketide Synthases from Alternaria cinerariae and Aspergillus terreus Highlights Key Structural Motifs

Chembiochem. 2015 Nov;16(17):2479-83. doi: 10.1002/cbic.201500428. Epub 2015 Oct 23.

Abstract

Iterative type I polyketide synthases (PKSs) from fungi are multifunctional enzymes that use their active sites repeatedly in a highly ordered sequence to assemble complex natural products. A phytotoxic macrolide with anticancer properties, 10,11-dehydrocurvularin (DHC), is produced by cooperation of a highly reducing (HR) iterative PKS and a non-reducing (NR) iterative PKS. We have identified the DHC gene cluster in Alternaria cinerariae, heterologously expressed the active HR PKS (Dhc3) and NR PKS (Dhc5) in yeast, and compared them to corresponding proteins that make DHC in Aspergillus terreus. Phylogenetic analysis and homology modeling of these enzymes identified variable surfaces and conserved motifs that are implicated in product formation.

Keywords: bioinformatics; biosynthesis; dehydrocurvularin; heterologous expression; polyketide.

Publication types

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

MeSH terms

  • Alternaria / enzymology*
  • Alternaria / genetics
  • Aspergillus / enzymology*
  • Aspergillus / genetics
  • Catalytic Domain
  • Multigene Family
  • Phylogeny
  • Polyketide Synthases / classification
  • Polyketide Synthases / genetics
  • Polyketide Synthases / metabolism*
  • Protein Structure, Tertiary
  • Zearalenone / analogs & derivatives*
  • Zearalenone / biosynthesis
  • Zearalenone / chemistry

Substances

  • dehydrocurvularin
  • Zearalenone
  • Polyketide Synthases