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.

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应用的分子进化来扩大生物学创建的蛋白质的能力。下一代生物技术将使用生活系统的组成部分来产生不自然的生物聚合物，包括含有不自然氨基酸的蛋白质。该奖项将在加深我们对活细胞中蛋白质的理解的同时发展这种生物技术。由生物技术生产的蛋白质可以在类似药品，化妆品，工业制造和洗衣清洁剂等产品中使用。将非天然氨基酸添加到这些氨基酸中可能会开放以探索具有天然蛋白无法达到的特性的蛋白质的地平线。该项目培训了本科生的尖端技术开发方法。为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结合在一起，以控​​制蛋白质体外合成的每个步骤。这包括开发新的方法，将不自然的氨基酸通过指向充电催化剂的导向演变，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，以及对翻译系统利用辅助因素来确定开始点和端的sernna sermernla sysermernna sysermernna sysermerna rna。 这些与X射线晶体学支持的核糖体模型结合在一起，以在此空间中构建合成生物学的复杂图像。