New Tools to Access the Fungal Metabolome and its Ecological Function

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With this?award, the Chemistry of Life Processes?Program in the Chemistry Division is supporting?Dr. Sandra Loesgen?from Oregon State University to examine the chemical structure and ecological function of compounds produced by fungi. Fungi are critical members of most ecosystems. Many fungi produce a diversity of secondary metabolites, chemical compounds that have important roles in their defense, communication between individuals of the same species, and communication between different species. Fungal secondary metabolites have also been used by humans for biomedical and agricultural applications, such as the antibiotic penicillin, the fungicide strobilurin, and the immunosuppressant cyclosporin. However, identifying these compounds and understanding their ecological function remains difficult and labor intensive. This research project aims to implement new approaches for isolating and studying the chemicals produced by fungi, using methods including gene activation and metabololite profiling. These experiments contribute to an improved understanding of the complex chemical ecology of fungi. This work also has potential to identify novel secondary metabolites with practical applications. The Loesgen Lab regularly participates in OSU's Discovery Days, a semiannual education fair that serves 3500 children from schools around Oregon. This project expands the lab's collaboration with the Oregon Museum of Science and Industry (OMSI) and establishes an interactive exhibit that introduces children and their parents to natural products chemistry. Microbial chemistry is an interdisciplinary field with important ecological applications, and is thus very well positioned to serve as a vehicle for chemistry education. This team participates in the Chemistry Undergraduate Mentorship and Empowerment (ChUME) Initiative atOSU. ChUME enhances undergraduate student success by providing students with a strong professional support network and personal mentoring.Three prominent challenges in modern microbial chemistry are driving expression of silenced gene clusters, identifying novel secondary metabolites, and understanding the ecological role of identified compounds. Dr. Loesgan and her group will study the environmental, chemical, and epigenetic perturbation in fungi to access previously repressed secondary metabolites. They will investigate metabolomics methods used to rapidly identify newly expressed natural products and integrate metabolomics methods with bioassay data to enable the elucidation of the ecological role of secondary metabolites. Aim 1 establishes a method for de-repressing gene clusters using a novel class of chemical epigenetic modifying agents. Aim 2 uses metabolomics methods to analyze liquid chromatography mass spectrometry (LCMS), high performance two-dimensional NMR, and RNA expression data in order to detect and isolate newly expressed secondary metabolites. Aim 3 tests secondary metabolites for effects on bacterial, fungal, and plant growth in order to determine the likely ecological role of these molecules.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.