STTR Phase I: Synthetic Biology 2.0: A platform for the automated design of cell factories incorporating synthetic enzymes

STTR 第一阶段：合成生物学 2.0：结合合成酶的细胞工厂自动化设计平台

• 批准号: 1321578
• 负责人: Alexandre Zanghellini
• 金额: $ 22.5万
• 依托单位: ARZEDA Corp.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1321578&HistoricalAwards=false
• 关键词: STTR; Phase; Synthetic; Biology; 2.0

This Small Business Technology Transfer (STTR) Phase I project brings together computational enzyme design with systems biology to create a fully integrated platform for novel pathway designs. The approach chosen will combine specific databases and a novel pathway synthesis tool. This computational tool will use the information present in the databases to automatically discover, or "design", novel pathways for fermenting natural renewable feedstock to virtually any chemical of human interest. In the Phase II Experimental Plan, the goal is to further advance the concept by developing a high-performance pathway prioritization module to estimate each designed pathway yield and impact on organism metabolism, and experimentally test the performance of the system. To our knowledge, the proposed research is the first attempt of combining computational enzyme design with computational pathway prospecting and modeling. The broader impact/commercial potential of this project, if successful, will be to engineer biosystems and cell factories for industrial applications, especially in the field of bio-based chemicals and biofuels. Most successes to date in the field of synthetic biology have involved recombining natural enzyme building blocks into novel pathways. However, recent developments in computational enzyme design make it possible to have designer enzymes to enhance nature's catalytic repertoire. Being able to have an automated, computer-aided design tool that leverages new capabilities to create novel metabolic pathways employing synthetic enzymes will bring us closer to truly synthetic biology.

这个小型企业技术转移（STTR）第一阶段项目将计算酶设计与系统生物学结合起来，为新途径设计创建一个完全集成的平台。所选择的方法将结合特定的数据库和一种新的途径合成工具。这个计算工具将利用数据库中的信息自动发现或“设计”新的途径，将天然可再生原料发酵成人类感兴趣的几乎任何化学物质。在第二阶段的实验计划中，我们的目标是进一步推进这一概念，开发一个高性能的途径优先级模块，以估计每个设计的途径的产量和对生物体代谢的影响，并实验测试系统的性能。据我们所知，这项研究是将计算酶设计与计算途径勘探和建模相结合的第一次尝试。这个项目如果成功，其更广泛的影响/商业潜力将是为工业应用设计生物系统和细胞工厂，特别是在生物基化学品和生物燃料领域。迄今为止，合成生物学领域的大多数成功都涉及到将天然酶构建块重组成新的途径。然而，计算酶设计的最新发展使设计酶能够增强自然的催化能力。能够拥有一个自动化的、计算机辅助的设计工具，利用新的能力来创造利用合成酶的新的代谢途径，将使我们更接近真正的合成生物学。