Angew. Chem. Int. Ed. 53, 4346–4349 (2014)

Credit: CYAGNX © DAVID MARK/ALAMY

Over the past two decades the European ash tree has been severely afflicted by a disease called ash dieback. Caused by the pathogenic fungus Hymenoscyphus pseudoalbidus, ash dieback is characterized by loss of leaves, necrotic lesions, suppression of new growth, and normally the eventual death of the tree. Regions affected by dieback have lost up to 90% of their ash trees and germination of new seeds is also inhibited by the fungus. The fungal metabolite viridiol — a known toxin — has been proposed as one of the virulence factors responsible. However, when isolated from different fungal strains the concentration of viridiol does not correlate with the pathogenicity of the fungi, suggesting that other molecules must also be involved.

Now, in an effort to discover more about the compounds responsible for the pathogenicity of this fungus, a team led by Jeroen S. Dickschat at Technische Universtität Braunschweig has analysed the volatile metabolites it produces. Their first step was to collect the metabolites released into the air. These compounds were then analysed by gas chromatography and identified by a combination of mass spectrometry and comparisons to reference compounds. Once the compounds' identities were known, the team tested their bioactivity using ash seeds germinated on agar. One volatile lactone, 3,4-dimethylpentan-4-olide, showed concentration-dependent bioactivity against ash. At higher concentrations this lactone completely inhibited germination and also caused necrotic lesions on the seeds.

The lactone contains a chiral centre, so the team synthesized both enantiomers to determine whether they had different activities. Surprisingly, the racemic mixture was found to be more potent than either enantiomer alone, although the reason for this is unclear as the molecular target of 3,4-dimethylpentan-4-olide is not known. Nevertheless this volatile lactone seems to be an important virulence factor; however, as with viridiol, it does not fully account for the toxic effects of ash dieback, because although the lactone was produced by most of the pathogenic fungal strains tested, it was not synthesized by all of them.