Evaluation of lysine biosynthesis as an antifungal drug target: biochemical characterization of Aspergillus fumigatus homocitrate synthase and virulence studies.

ABSTRACT: Aspergillus fumigatus is the main cause of severe invasive aspergillosis. To combat this life-threatening infection, only limited numbers of antifungals are available. The fungal alpha-aminoadipate pathway, which is essential for lysine biosynthesis, has been suggested as a potential antifungal drug target. Here we reanalyzed the role of this pathway for establishment of invasive aspergillosis in murine models. We selected the first pathway-specific enzyme, homocitrate synthase (HcsA), for biochemical characterization and for study of its role in virulence. A. fumigatus HcsA was specific for the substrates acetyl-coenzyme A (acetyl-CoA) and alpha-ketoglutarate, and its activity was independent of any metal ions. In contrast to the case for other homocitrate synthases, enzymatic activity wa

SUBMITTER: Schobel F 

PROVIDER: S-EPMC2901645 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature