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.

这个项目是由数学和物理科学局化学部的生命过程化学计划和生物科学局分子和细胞生物科学部的分子遗传机制群共同资助的。通过这个奖项，化学部的生命过程化学计划资助了应用分子进化基金会内韦斯海默科学与技术研究所(TWIST)的史蒂文·本纳博士，以扩大生物创造蛋白质的能力。下一代生物技术将使用生命系统的组件来创造非天然的生物聚合物，包括含有非天然氨基酸的蛋白质。这一奖项将发展这一生物技术，同时加深我们对蛋白质是如何在活细胞中制造的理解。生物技术生产的蛋白质可用于制药、化妆品、工业制造和洗涤剂等多种产品。将非天然氨基酸添加到这些蛋白质中，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天地。该项目对本科生进行尖端技术开发方法的培训。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相结合，以控制蛋白质体外合成的每一步。这包括开发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分子上的新方法，通过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诚，以及理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。这些与核糖体模型相结合，最近得到了X射线结晶学的支持，在这个空间建立了一幅合成生物学的复杂图景。