New Tools to Access the Fungal Metabolome and its Ecological Function

有了这一奖项，化学系的生命过程化学项目支持俄勒冈州立大学的桑德拉·洛斯根博士研究真菌产生的化合物的化学结构和生态功能。真菌是大多数生态系统的重要成员。许多真菌产生各种各样的次生代谢产物，这些化合物在它们的防御、同一物种的个体之间的沟通以及不同物种之间的沟通中发挥着重要的作用。真菌次生代谢物也被人类用于生物医学和农业应用，如抗生素青霉素、杀菌剂Strobilurin和免疫抑制剂环孢菌素。然而，识别这些化合物并了解它们的生态功能仍然是困难和劳动密集型的。这项研究项目旨在利用基因活化和代谢物图谱等方法，实施分离和研究真菌产生的化学物质的新方法。这些实验有助于更好地理解真菌的复杂化学生态。这项工作还具有鉴定具有实际应用价值的新型次生代谢物的潜力。洛斯根实验室定期参加俄亥俄州立大学的发现日活动，这是一个每半年举办一次的教育博览会，服务于俄勒冈州周围学校的3500名儿童。该项目扩大了该实验室与俄勒冈州科学与工业博物馆(OMSI)的合作，并建立了一个互动展览，向儿童及其父母介绍天然产品化学。微生物化学是一个具有重要生态学应用的跨学科领域，因此非常适合作为化学教育的载体。这个团队参与了俄亥俄州立大学的化学本科生辅导和授权倡议(CHUME)。Chume通过为学生提供强大的专业支持网络和个人指导来提高本科生的成功。现代微生物化学中的三个突出挑战是推动沉默基因簇的表达，识别新的次生代谢物，以及理解已识别化合物的生态作用。Loesgan博士和她的团队将研究真菌中的环境、化学和表观遗传扰动，以获得以前被抑制的次生代谢物。他们将研究用于快速鉴定新表达的天然产物的代谢组学方法，并将代谢组学方法与生物测定数据相结合，以阐明次生代谢物的生态作用。目的1建立一种利用一类新型化学表观遗传修饰剂去抑制基因簇的方法。目的2利用代谢组学方法分析液-质联用、高效二维核磁共振和RNA表达数据，以检测和分离新表达的次生代谢物。AIM 3测试次生代谢物对细菌、真菌和植物生长的影响，以确定这些分子可能的生态作用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.