Natural Product Biosynthesis in Lichen and Other Fungi

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The identification of novel biologically active natural products is key to the long-term development of new clinical treatments for infections and disease. The Sorensen Natural Products Laboratory at the University of Manitoba is examining the production of natural products by unique strains of lichen and fungi from Northern Manitoba. Have started to develop a detailed understanding of the biosynthesis of the antibacterial and antifungal lichen natural product usnic acid. We will use molecular biology techniques to identify the genes, and thereby the enzymes, that are involved in the biosynthesis of usnic acid. This proposal describes how we will use this knowledge to produce natural product analogues with improved biological activity. This proposal will also describe how our research program will discover new natural products with antibacterial activity. We describe in this proposal how we will screen novel strains of fungi from Northern Manitoba for the production of new antibiotic natural products. New molecules with good bioactivity profiles can be further examined for their development into clinical antibiotics. The new structures identified will also serve as the inspiration for further biosynthetic studies. This research program is at the forefront of natural products research by developing a complete picture at the genetic level of how biologically active natural products are synthesized in Nature. The fudnign requested in this proposal will support three Ph.D. students and 10 undergraduate summer students. The students and other researchers that are given the opportunity to work in this research environment will find a fertile training ground to learn the latest techniques in a modern facility. These highly qualified personnel will be exceptionally placed for high impact careers in the pharmaceutical industry as well as in academia. The long term economic impact of this research will provide a benefit to Canada as industrial partners look to commercialize the lead compounds identified by this program.