Location: Cereal Disease LabTitle: Cellular development associated with induced secondary metabolism in the filamentous fungus Fusarium graminearum) Author
Submitted to: PLoS Pathogens
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/28/2013
Publication Date: 5/7/2013
Citation: Menke, J., Weber, J., Broz, K.L., Kistler, H.C. 2013. Cellular development associated with induced secondary metabolism in the filamentous fungus Fusarium graminearum. PLoS Pathogens. 8(5):e63077. Interpretive Summary: Certain fungi cause diseases of wheat and barley crops and may infest the grain with harmful metabolites. The fungus Fusarium graminearum contaminates these grains with a compound known as deoxynivalenol (DON) or vomitoxin, whose presence in the human diet is a food safety concern. Our previous studies have shown that the fungus is remarkably adapted for producing vomitoxin by precisely regulating the genes for its synthesis in order to promote toxin accumulation in plants. We have now found, by labeling proteins for toxin synthesis with fluorescent proteins, that these proteins are directed to subcellular toxin factories; small vesicles called toxisomes that appear to serve as the staging area for the toxin biosynthetic assembly line. When cell culture conditions are changed in order to promote toxin biosynthesis, another pathway supplying precursor molecules for toxin synthesis may be shifted within the cell to toxisomes, streamlining the path to toxin synthesis. By making toxin in a confined vesicle within the cell, the fungus may protect itself from the inhibitory effects of its own toxin and may allow for an efficient way to deliver it to the plant. This study establishes that toxin synthesis requires a complex developemntal event which ultimately determines the outcome of plant infection and plant health. This information will be helpful to plant improvement specialists who are working to develop plants resistant to these toxins or for developing novel strategies for emelioration of the effects of these toxins.
Technical Abstract: Several species of the filamentous fungus Fusarium colonize plants and produce toxic small molecules that contaminate agricultural products, rendering them unsuitable for consumption. Among the most destructive of these species is F. graminearum, which causes disease in wheat and barley and often infests the grain with harmful trichothecene mycotoxins. Synthesis of these secondary metabolites is induced during plant infection or in culture in response to chemical signals. Our results show that trichothecene biosynthesis involves a complex developmental process that includes dynamic changes in cell morphology and the biogenesis of novel subcellular structures. Two cytochrome P-450 oxygenases (Tri4p and Tri1p) involved in early and late steps in trichothecene biosynthesis were tagged with fluorescent proteins and shown to co-localize to vesicles we named "toxisomes". Toxisomes, the inferred site of trichothecene biosynthesis, dynamically interact with motile vesicles containing a predicted major facilitator superfamily protein (Tri12p) previously implicated in trichothecene export and tolerance. The immediate isoprenoid precursor of trichothecenes is the primary metabolite farnesyl pyrophosphate. Changes occur in the cellular localization of the isoprenoid biosynthetic enzyme HMG CoA reductase when trichothecene non-induced cultures are transferred either to trichothecene inducing or non-inducing media. Initially localized in the cellular endomembrane system, HMG CoA reductase, upon trichothecene induction, increasingly is targeted to toxisomes. Metabolic pathways of primary and secondary metabolism thus may be coordinated and co-localized under conditions when trichothecene synthesis occurs.