Natural Product Biosynthesis in Lichen and Other Fungi

新型生物活性天然产物的鉴定是感染和疾病新临床治疗方法长期开发的关键。马尼托巴大学的索伦森天然产物实验室正在研究来自马尼托巴北方的独特地衣和真菌菌株的天然产物生产。已经开始对抗菌和抗真菌地衣天然产物松萝酸的生物合成有了详细的了解。我们将使用分子生物学技术来鉴定基因，从而确定参与松萝酸生物合成的酶。该提案描述了我们将如何利用这些知识来生产具有改善生物活性的天然产物类似物。 该提案还将描述我们的研究计划将如何发现具有抗菌活性的新天然产物。我们在本提案中描述了我们将如何筛选来自北方马尼托巴的新型真菌菌株，用于生产新的抗生素天然产物。具有良好生物活性的新分子可以进一步研究，以开发成临床抗生素。新发现的结构也将为进一步的生物合成研究提供灵感。该研究计划是天然产物研究的前沿，通过在基因水平上开发生物活性天然产物在自然界中如何合成的完整图片。本提案中要求的fudnign将支持三个博士学位。学生和10名本科暑期学生。有机会在这种研究环境中工作的学生和其他研究人员将找到一个肥沃的训练场，在现代化的设施中学习最新的技术。这些高素质的人才将被特别安置在制药行业以及学术界的高影响力职业。这项研究的长期经济影响将为加拿大带来好处，因为工业合作伙伴希望将这项计划确定的先导化合物商业化。

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.