Function and engineering of fungal biosynthetic genes

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Fungi are found in nearly every environment. They commonly produce diverse small molecule natural products, many of which mediate interactions between organisms or potently target proteins. Fungal natural products fall into many different chemical subtypes and thus represent a resource for new chemical building blocks. In particular, fungal polyketides and peptides have a very rich chemistry. Genetic methods provide a possible route both to rapidly identify new natural products and to use fungal chemical building blocks in the chemical synthesis of new molecules.The Schmidt group is applying a two-pronged approach to solve this problem using the fungal biosynthetic protein, equisetin synthetase, as a model system. First, a series of biochemical experiments is aimed at elucidating function of the equisetin synthetase protein. Second, an interdisciplinary approach linking chemical output directly to gene sequence is under development. This new method is designed to solve the selectivity problem and to provide a new tool set that will be broadly useful in chemical biology. Gene sequences and chemical products will be rapidly compared in a novel high-throughput fashion. Through this approach, new genes will be cloned from numerous sources, new structures will be made by genetic engineering, and new insights will be achieved linking gene sequence to structure in the fungal polyketide and peptide groups.Broader Impacts. On the scientific and training side, the PI will develop innovative new tools that will be broadly useful in chemical biology and will train graduates and undergraduates from basic science and cross-disciplinary programs in interdisciplinary research. In outreach, he will work with a local high school that is economically and socially diverse. He will participate in a summer research program and will integrate some of his aims into a high school project entitled "Metagenomes in the community". Students will homology clone and compare fungal biosynthetic genes that are expressed in plants and other surfaces in their yards, parks, nearby wilderness areas, and so on. In turn, he will select some of these genes for later biochemical analysis by graduate students in partnership with these high school students. Emphasis will be placed on encouraging underrepresented students to pursue science in college and future careers.