Epidithiodiketopiperazine biosynthesis: a four-enzyme cascade converts glutathione conjugates into transannular disulfide bridges

Angew Chem Int Ed Engl. 2013 Oct 11;52(42):11092-5. doi: 10.1002/anie.201305059. Epub 2013 Aug 26.

Abstract

Enzyme quartet: Isolation of the first sulfur-bearing intermediate of the gliotoxin pathway in Aspergillus fumigatus and successful in vitro conversion of the bisglutathione adduct into an intact epidithiodiketopiperazine by a four-enzyme cascade (including glutamyltransferase GliK and dipeptidase GliJ) revealed an outstanding adaptation of a primary metabolic pathway into natural product biosynthesis that is widespread in fungi.

Keywords: Aspergillus fumigatus; biosynthesis; dipeptidase; gliotoxin; mycotoxins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus fumigatus / enzymology
  • Aspergillus fumigatus / metabolism*
  • Dipeptidases / metabolism
  • Disulfides / metabolism*
  • Gliotoxin / biosynthesis
  • Gliotoxin / metabolism
  • Glutathione / biosynthesis
  • Glutathione / metabolism*
  • Models, Molecular
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Piperazines / metabolism*

Substances

  • Disulfides
  • Piperazines
  • epidithiodiketopiperazine
  • Gliotoxin
  • Dipeptidases
  • dipeptidase
  • Glutathione