Clustered genes common to both Aspergillus fumigatus and ergot fungi control early steps within the ergot alkaloid pathway

• Published in: Phytopathology 2008-06, Vol.98 (6), p.S214-S214
• Main Authors: Coyle, C M, Goetz, KE, Panaccione, D G
• Format: Article
• Language: English
• Subjects: Aspergillus fumigatus; Claviceps purpurea; Neotyphodium
• ISSN: 0031-949X

Ergot alkaloids are mycotoxins that affect humans and animals through their interactions with multiple classes of monoamine receptors. They were discovered and have been studied extensively in the ergot fungus, Claviceps purpurea. Ergot alkaloids also have been reported in some closely related fungi, such as Neotyphodium spp. endophytes of grasses. Surprisingly, a different set of ergot alkaloids are produced by the distantly related fungus Aspergillus fumigatus, a common saprophyte and opportunistic pathogen of humans. We hypothesize that the ergot pathways of A. fumigatus and the ergot fungi share early steps and then diverge after the biosynthesis of the important intermediate compound, chanoclavine. A homologue of the gene (dmaW) encoding dimethylallyltryptophan synthase, which catalyzes the first step in the ergot alkaloid pathway of the Neotyphodium spp., was found in the A. fumigatus genome. Knockout of this gene via homologous recombination rendered a mutant that lacked ergot alkaloids. Aspergillus fumigatus dmaW is part of a cluster of genes that resemble genes clustered with dmaW in the ergot fungi. These genes may encode early, shared steps in the ergot alkaloid pathway. Four of these genes, easA, easC, easE, and easF, were knocked out; each mutation altered the profile of ergot alkaloids in A. fumigatus. Three of the mutants were blocked prior to chanoclavine, whereas one accumulated chanoclavine but not ergot alkaloids from the latter part of the pathway. The data indicate that the ergot alkaloid pathways of A. fumigatus and the ergot fungi share common early steps before diverging to produce different end products. Knockout mutants lacking ergot alkaloids will be valuable for testing the role of these toxins in animal pathogenesis and toxicoses. Characterization of the ergot alkaloid pathway and the ability to control the spectrum of alkaloids produced may lead to advances in the agricultural and medical fields.