Resistance is not futile: gliotoxin biosynthesis, functionality and utility

Trends Microbiol. 2015 Jul;23(7):419-28. doi: 10.1016/j.tim.2015.02.005. Epub 2015 Mar 10.

Abstract

Gliotoxin biosynthesis is encoded by the gli gene cluster in Aspergillus fumigatus. The biosynthesis of gliotoxin is influenced by a suite of transcriptionally-active regulatory proteins and a bis-thiomethyltransferase. A self-protection system against gliotoxin is present in A. fumigatus. Several additional metabolites are also produced via the gliotoxin biosynthetic pathway. Moreover, the biosynthesis of unrelated natural products appears to be influenced either by gliotoxin or by the activity of specific reactions within the biosynthetic pathway. The activity of gliotoxin against animal cells and fungi, often mediated by interference with redox homeostasis or protein modification, is revealing new metabolic interactions within eukaryotic systems. Nature has provided a most useful natural product with which to reveal some of its many molecular secrets.

Keywords: Aspergillus fumigatus; NRPS; antioxidant; natural products; secondary metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aspergillus fumigatus / genetics
  • Aspergillus fumigatus / metabolism*
  • Aspergillus fumigatus / pathogenicity*
  • Biological Products / metabolism
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal
  • Gliotoxin / biosynthesis
  • Gliotoxin / chemistry
  • Gliotoxin / metabolism*
  • Gliotoxin / pharmacology
  • Metabolome / physiology
  • Multigene Family

Substances

  • Biological Products
  • Fungal Proteins
  • Gliotoxin