Collaborative Research: Designing a Minimized Genome Cyanobacterial Chassis for Efficient Bioproduction

该项目的目标是获得一个光合生物生产平台，通过从蓝藻中反复去除选定的基因，可以有效地将阳光和二氧化碳转化为感兴趣的生物产品。蓝藻是一种氧气光合作用的原核生物，具有独特的优势，可以成为利用阳光和大气二氧化碳以及免费和无处不在的底物进行可持续生物生产的最佳平台。选择去除的基因将借助计算方法和基因编辑技术进行识别。在不影响生物体生长速度的情况下完成基因去除。本项目通过不同的合作项目，培养多名国内外本科生，学习分子工具的设计与实现、相关计算技术和光合生物生理学。此外，该项目旨在与各种科学创业企业保持一致。在实验分析和代谢模型的指导下，该项目通过多步骤的基因组编辑技术，将聚球菌2973（一种迄今为止观察到的光自养生长最快的蓝藻）简化为理想的底盘菌株。减少的效果是通过插入报告通路的生长速度和生产力来评估的。在保持快速生长的同时最小化基因组减轻了菌株的代谢负担，消除了挑战可预测工程的隐调控过程，并提高了对这种强大的自养驮马的理解和控制。创造一种新型流线型蓝藻模型是实现工业“绿色大肠杆菌”和为可持续生物经济奠定基础的重要一步。该奖项由分子和细胞生物科学部的系统和合成生物学集群以及化学、生物工程、环境和运输系统部的细胞和生化工程项目共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The goal of this project is to obtain a photosynthetic bioproduction platform that can efficiently convert sunlight and CO2 into bioproducts of interest, through iterative removal of selected genes from a cyanobacterium. Cyanobacteria are oxygenic photosynthetic prokaryotes that are uniquely poised to become optimal platforms for sustainable bioproduction using sunlight and atmospheric CO2 as well as free and ubiquitous substrates. The genes selected for removal would be identified with the aid of computational methods and gene editing techniques. Gene removal is accomplished without compromising the growth rate of the organism. This project trains several national and international undergraduate students under different collaborative programs, in the design and implementation of molecular tools, relevant computational techniques and physiology of photosynthetic organisms. In addition, the project is designed to align with a variety of scientific entrepreneurial ventures. This project develops Synechococcus 2973, a cyanobacterium displaying the fastest photoautotrophic growth ever observed, into an ideal chassis strain by streamlining its genome in a multi-step process that involves state-of-the-art genome-editing technology, guided by experimental analysis and metabolic modeling. Efficacy of reduction is assessed by both growth rate and productivity of a plug-in reporter pathway. Minimizing the genome while retaining fast growth eases the metabolic burden on the strain, removes cryptic regulatory processes that challenge predictable engineering, and improves understanding and control over this powerful autotrophic workhorse. The creation of a novel streamlined model cyanobacterium is a significant step in achieving an industrial “green E. coli” and establishing the foundation for a sustainable bioeconomy.This award is co-funded by the Systems and Synthetic Biology Cluster in the Division of Molecular and Cellular Biosciences and the Cellular and Biochemical Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.