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.

在几乎每个环境中都发现了真菌。它们通常会产生多种小分子天然产物，其中许多产物介导生物之间的相互作用或有效靶向蛋白质。真菌天然产品属于许多不同的化学亚型，因此代表了新的化学构建块的资源。特别是，真菌聚酮化合物和肽具有非常丰富的化学作用。遗传学方法提供了一种可能迅速识别新天然产品的可能途径，并在新分子的化学合成中使用真菌化学构建块。SchmidtGroup采用两种普通的方法来使用真菌生物合成蛋白，Equisetetin nettase解决此问题，作为模型系统。首先，一系列的生化实验旨在阐明奎汀合成酶蛋白的功能。其次，将化学输出与基因序列直接联系起来的跨学科方法正在开发中。这种新方法旨在解决选择性问题，并提供一个在化学生物学中广泛有用的新工具集。基因序列和化学产品将以新型的高通量方式迅速比较。通过这种方法，将从众多来源克隆新的基因，基因工程将制造新的结构，并将实现新的见解，将基因序列与真菌聚酮化合物和肽组的结构联系起来。在科学和培训方面，PI将开发创新的新工具，这些新工具将在化学生物学中广泛有用，并将在跨学科研究中培训基础科学和跨学科计划的毕业生和本科生。在宣传中，他将与一所在经济和社会上多样化的当地高中合作。他将参加夏季研究计划，并将他的一些目标纳入一个名为“社区中的元基因组”的高中项目。学生将同源性克隆并比较在其院子，公园，附近的荒野地区等在植物和其他表面上表达的真菌生物合成基因。反过来，他将与这些高中生合作，选择其中一些基因进行以后的生化分析。重点将放在鼓励代表性不足的学生从事大学和未来职业的科学方面。