Function and engineering of fungal biosynthetic genes

真菌生物合成基因的功能与工程

• 批准号: 0957791
• 负责人: Eric Schmidt
• 金额: $ 48万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0957791&HistoricalAwards=false
• 关键词: Function; engineering; fungal; biosynthetic; genes

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.

真菌几乎存在于每一种环境中。它们通常产生不同的小分子天然产物，其中许多调节生物体之间的相互作用或有效地针对蛋白质。真菌天然产物分为许多不同的化学亚型，因此是新的化学成分的来源。尤其是真菌多酮和多肽具有非常丰富的化学成分。遗传方法提供了一种可能的途径，既可以快速鉴定新的天然产物，也可以使用真菌化学构件来化学合成新分子。施密特小组正在采用双管齐下的方法来解决这个问题，使用真菌生物合成蛋白-木犀草素合成酶作为模型系统。首先，进行了一系列的生化实验，以阐明木犀草素合成酶蛋白的功能。其次，一种将化学产出直接与基因序列联系起来的跨学科方法正在开发中。这种新的方法旨在解决选择性问题，并提供一种新的工具集，将在化学生物学中广泛使用。基因序列和化学产品将以一种新的高通量方式进行快速比较。通过这种方法，将从众多来源克隆新的基因，通过基因工程制造新的结构，并将获得将基因序列与真菌多酮和多肽类的结构联系起来的新见解。在科学和培训方面，PI将开发将在化学生物学中广泛使用的创新新工具，并将培训基础科学和跨学科项目的毕业生和本科生进行跨学科研究。在外展方面，他将与当地一所经济和社会多元化的高中合作。他将参加一个暑期研究计划，并将把他的一些目标整合到一个名为《社区中的元基因组》的高中项目中。学生们将同源克隆和比较在他们院子、公园、附近荒野地区的植物和其他表面表达的真菌生物合成基因。反过来，他将选择其中的一些基因，供研究生与这些高中生合作进行以后的生化分析。重点将放在鼓励未被充分代表的学生在大学和未来的职业生涯中追求科学。