Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis

Angew Chem Int Ed Engl. 2016 Jun 1;55(23):6784-8. doi: 10.1002/anie.201511882. Epub 2016 Apr 21.

Abstract

Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9-membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate-processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine-binding proteins.

Keywords: biosynthesis; cyclization; enzymes; maleidride; polyketides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus oryzae / genetics
  • Aspergillus oryzae / metabolism
  • Chromatography, High Pressure Liquid
  • Cyclization
  • Fungi / metabolism*
  • Furans / chemistry
  • Furans / metabolism
  • Hydrolases / genetics
  • Hydrolases / metabolism
  • Maleic Anhydrides / chemistry
  • Maleic Anhydrides / metabolism*
  • Mass Spectrometry
  • Multigene Family
  • Polyketide Synthases / genetics
  • Polyketide Synthases / metabolism

Substances

  • Furans
  • Maleic Anhydrides
  • byssochlamic acid
  • Polyketide Synthases
  • Hydrolases