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Natural products: metabolic engineering and discovery of novel compounds and enzymes

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Natural products from plants, fungi, and bacteria are an invaluable source of bioactive compounds with numerous applications in the pharmaceutical industry and agriculture. Metabolic engineering can be utilized to increase the yield of these valuable compounds and their precursors. Meanwhile, genome mining can be employed to discover novel natural product scaffolds and unique functional groups that can confer various biological activities to the resulting compound. During my doctoral research, I have performed work in both of these fields to engineer yeast for precursor production of the pharmaceutically relevant monoterpene indole alkaloids as well as elucidate the biosynthesis of new natural products from several fungal species. Strategies for yeast metabolic engineering included targeting the production of monoterpene precursors to the mitochondria and further mitochondrial engineering through deletion of transporter genes and transcription factor overexpression. Genome mining efforts led to the discovery of new compounds with a unique hybrid terpene and amino acid derived scaffold as well as a new family of biosynthetic core genes that form arginine containing cyclodipeptides. Study of these pathways also resulted in the identification of enzymes that can perform novel reactions to create greater chemical diversity. These genes can expand the query database to mine for more compounds with novel structures.

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This item is under embargo until June 9, 2024.