Protostadienol biosynthesis and metabolism in the pathogenic fungus Aspergillus fumigatus

Org Lett. 2009 Mar 19;11(6):1241-4. doi: 10.1021/ol802696a.

Abstract

Details of the fungal biosynthetic pathway to helvolic acid and other fusidane antibiotics remain obscure. During product characterization of oxidosqualene cyclases in Aspergillus fumigatus, we found the long-sought cyclase that makes (17Z)-protosta-17(20),24-dien-3beta-ol, the precursor of helvolic acid. We then identified a gene cluster encoding the pathway to helvolic acid, which is controlled by a transcription regulator (LaeA) associated with fungal virulence. Evidence regarding the evolutionary origin and taxonomic distribution of fusidane biosynthesis is also presented.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification*
  • Anti-Bacterial Agents / pharmacology
  • Aspergillus fumigatus* / chemistry
  • Aspergillus fumigatus* / genetics
  • Aspergillus fumigatus* / metabolism
  • Fusidic Acid / analogs & derivatives*
  • Fusidic Acid / chemistry
  • Fusidic Acid / isolation & purification
  • Fusidic Acid / pharmacology
  • Intramolecular Transferases / genetics
  • Intramolecular Transferases / metabolism*
  • Molecular Structure
  • Stereoisomerism
  • Triterpenes / chemistry
  • Triterpenes / isolation & purification*

Substances

  • Anti-Bacterial Agents
  • Triterpenes
  • protosta-13(17),24-dien-3beta-ol
  • Fusidic Acid
  • Intramolecular Transferases
  • lanosterol synthase
  • helvolic acid