GliT a novel thiol oxidase implications in self resistance and biosynthesis of gliotoxin.

D.H. Scharf1, N. Remme2, T. Heinekamp1, P. Hortschansky1, A.A. Brakhage1 ,3, C. Hertweck2 ,3

Author address: 

1Leibniz Institute for Natural Product Research and Infection Biology, Dept. Molecular and Applied Microbiology 2Leibniz Institute for Natural Product Research and Infection Biology, Dept. Biomolecular Chemistry 3Friedrich Schiller University of Jen

Abstract: 

Aspergillus fumigatus and other pathogenic fungi have developed various chemical strategies to distress, weaken or even kill their plant or animal hosts. In invasive aspergillosis, the leading cause for death in immunocompromised patients, the fungal secondary metabolite gliotoxin plays a critical role for virulence. Gliotoxin is the prototype of a small family of epipolythiodioxopiperazines (ETPs), which features unique transannular di- or polysulfide bridges. Extensive molecular studies have revealed that this rare structural motif is indispensable for bioactivity and is the key to the deleterious effects of gliotoxin. Here, we describe the function of GliT, an enzyme of the gliotoxin biosynthesis pathway. We could reveal the activity of GliT both in vivo by means of feeding experiments and in vitro by heterologous overproduction and further biochemical characterisation of GliT. We proved that GliT is essential for biosynthesis of gliotoxin and therefore may play a critical role in virulence of A. fumigatus. Furthermore, GliT confers self resistance of A. fumigatus against gliotoxin. These investigations led to the discovery of an entirely new mechanism how microorganisms could prevent self poisoning by their own toxins. References: Scharf D. H., et al. (2010) J. Am. Chem. Soc. Schrettl M., et al. (2010) PLoS Pathog.
2011

abstract No: 

NULL

Full conference title: 

26th Fungal Genetics Conference
    • Fungal Genetics Conference 26th (2005)