Secret arsenal of a cereal killer- cryptic activation of secondary metabolism biosynthesis in Fusarium graminearum

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Shostak, Kristina




Fusarium graminearum is a fungal pathogen and is a major causal agent of diseases in several agriculturally important crop species. In addition to the disease that diminishes grain yield, this pathogen produces secondary metabolites that are harmful to both plants and animals. Secondary metabolites are not essential for survival, instead, they enable the pathogen to successfully infect its host. In fungi, genes necessary to produce secondary metabolites are often arranged together in the genome, forming secondary metabolic clusters (SMCs). The F. graminearum genome contains 76 such clusters with a potential to produce a diverse array of secondary metabolites (SMs). However, given high functional specificity and energetic cost, most of these clusters remain silent, or "cryptic," unless the organism is subjected to an environment conductive to SM production. Alternatively, SMCs can be activated by genetically manipulating their activators or repressors. The goal of this dissertation is to establish the transcriptional factor TRI6 and the MAP kinase MGV1 as regulators of secondary metabolism by genetically altering their expression and thus activating cryptic SMCs in F. graminearum. TRI6 is a transcriptional factor that regulates the trichothecene group of mycotoxins and other non-trichothecene genes. MGV1 is a MAP kinase, implicated in regulation of diverse cellular responses, including secondary metabolite biosynthesis. We used transcriptomic and metabolomic analyses to identify SMCs regulated by TRI6 and MGV1. We discovered that at the transcriptional level, MGV1 and TRI6 co-regulate biosynthesis of four SMs; however, MGV1 also exerts its control of three SMCs at the post-transcriptional level. Finally, at the mechanistic level, we demonstrate that TRI6 regulates the trichothecene genes by directly binding to the promoters of the genes of the cluster. However, the regulation of other SMCs such as gramillin is achieved indirectly, through physical binding of TRI6 to the cluster-specific protein GRA2.


Biology - Molecular




Carleton University


John Vierula
Indira Thapa
David Overy
Nora Foroud
Christopher Bonner
Barbara Blackwell

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Theses and Dissertations

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