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

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在一起，为新的途径设计创建了一个完全集成的平台。选择的方法将结合特定的数据库和一个新的途径合成工具。这一计算工具将利用数据库中的信息自动发现或“设计”将天然可再生原料发酵成几乎任何人类感兴趣的化学品的新途径。在第二阶段实验计划中，目标是通过开发高性能的路径优先模块来进一步推进这一概念，以估计每条设计的路径的产量和对生物体新陈代谢的影响，并通过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探索和建模相结合的第一次尝试。该项目如果成功，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，特别是在生物化学品和生物燃料领域。到目前为止，合成生物学领域的大多数成功都涉及将天然酶构建块重新组合成新的途径。然而，最近在计算酶设计方面的发展使设计酶来增强自然的催化能力成为可能。能够拥有一种自动化的、计算机辅助的设计工具，利用新的能力来利用合成酶创造新的代谢途径，将使我们更接近真正的合成生物学。

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.