CAREER: Design, Construction, and Validation of Modular Chassis Cells for Efficient Combinatorial Biosynthesis of Chemicals

从可再生原料生产工业化学品的新型生物衍生平台的快速发展需要开发创新的新工具。该项目的总体目标是将模块化分子设计原则纳入微生物制造平台，以实现从易于互换的遗传模块高效合成目标化学品。该项目的成功将推进合成生物学和代谢工程的前沿，推进生物制造，培养大批本科生和研究生成为创新者和领导者，并通过实践经验让K-12学生接触STEM学科。该项目将解决三个基本问题：什么是模块化细胞？ 如何使用可交换模块从最小细胞构建微生物制造平台，以高效组合生物合成新化学品？ 什么类型的模块特别适合与建议的模块化单元耦合？ 首先，将开发MOCELL计算工具，以帮助设计和实施几个微生物生物合成平台。其次，这些MODCELL平台将在引入编码特定发酵途径酶的可交换模块后进行测试。 第三，MODCELL设计将被实验验证用于靶向酯的有效组合生物合成。

The envisioned rapid development of novel, biology-derived platforms for the production of industrial chemicals from renewable feedstocks requires the development of innovative new tools. The overarching goal of this project is to incorporate modular molecular design principles into microbial manufacturing platforms to enable the highly efficient synthesis of targeted chemicals from easily interchangeable genetic modules. The success of the project will advance frontiers of synthetic biology and metabolic engineering, advance biomanufacturing, train a large cohort of undergraduate and graduate students as innovators and leaders as well as expose K-12 students to STEM disciplines through hands-on experiences.This project will address three fundamental questions: What is a modular cell? How can microbial manufacturing platforms be constructed from a minimal cell using exchangeable modules for the highly efficient combinatorial biosynthesis of novel chemicals? What classes of modules are particularly suitable to couple with the proposed modular cell? First, MOCELL computational tools will be developed to aid the design and implementation of several microbial biosynthetic platforms. Second, these MODCELL platforms will be tested after introduction of exchangeable modules that encode enzymes for specific fermentative pathways. Third, The MODCELL design will be experimentally validated for efficient combinatorial biosynthesis of targeted esters.