Increasing Amino Acid Diversity in In Vitro Translation with Expanded Genetic Alphabets

通过扩展遗传字母表增加体外翻译中的氨基酸多样性

• 批准号: 1507816
• 负责人: Steven Benner
• 金额: $ 48万
• 依托单位: Foundation for Applied Molecular Evolution, Inc.
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1507816&HistoricalAwards=false
• 关键词: Increasing; Amino; Acid; Diversity; Vitro

This project is jointly funded by the Chemistry of Life Processes Program in the Division of Chemistry in the Directorate of Mathematical and Physical Sciences and the Molecular Genetic Mechanisms Cluster in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Steven Benner of The Westheimer Institute for Science and Technology (TWIST) within the Foundation for Applied Molecular Evolution to expand the power of biologically created proteins. The next generation of biotechnology will use components of living systems to create unnatural biopolymers, including proteins that contain unnatural amino acids. This award will develop this biotechnology, at the same time as deepening our understanding of how proteins are made in living cells. Proteins produced by biotechnology find use in products as diverse as pharmaceuticals, cosmetics, industrial manufacture, and laundry detergents. Adding unnatural amino acids to these may open up for exploration a horizon of proteins having properties that natural proteins cannot reach. The project trains undergraduate students in methods of cutting-edge technology development.The experiments designed for this project combine chemical synthesis with molecular biology, laboratory evolution, and bioinformatics to gain control over each step in the in vitro synthesis of proteins. This includes developing new ways to put unnatural amino acids onto unnatural transfer RNA molecules by directed evolution of charging catalysts, chemically synthesizing new nucleic acid analogs to manage infidelity in RNA biosynthesis and translation, and understanding of how translation systems exploit auxiliary factors to determine the starting point and ending point of messenger RNA translation. These are coupled with models for the ribosome, recently supported by X-ray crystallography, to build a complex picture of synthetic biology in this space.

该项目由数学和物理科学局化学司生命过程化学项目和生物科学局分子和细胞生物科学司分子遗传机制集群联合资助。化学部生命过程化学项目将资助韦斯特海默科学技术研究所 (TWIST) 的 Steven Benner 博士 应用分子进化来扩展生物产生的蛋白质的力量。下一代生物技术将利用生命系统的组成部分来制造非天然生物聚合物，包括含有非天然氨基酸的蛋白质。该奖项将开发这种生物技术，同时加深我们对活细胞中蛋白质如何制造的理解。通过生物技术生产的蛋白质可用于药品、化妆品、工业制造和洗衣粉等多种产品。在其中添加非天然氨基酸可能会为探索具有天然蛋白质无法达到的特性的蛋白质开辟新的视野。该项目对本科生进行前沿技术开发方法的培训。该项目设计的实验将化学合成与分子生物学、实验室进化和生物信息学相结合，以控制蛋白质体外合成的每个步骤。这包括开发新方法，通过电荷催化剂的定向进化将非天然氨基酸置于非天然转移RNA分子上，化学合成新的核酸类似物来管理RNA生物合成和翻译中的不忠实性，以及了解翻译系统如何利用辅助因素来确定信使RNA翻译的起点和终点。 这些与最近得到 X 射线晶体学支持的核糖体模型相结合，构建了该领域合成生物学的复杂图景。