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

该项目的目标是通过迭代移除蓝藻中选定的基因，获得一个能够有效地将阳光和二氧化碳转化为感兴趣的生物产品的光合作用生物生产平台。蓝藻是一种产氧的光合原核生物，利用阳光和大气中的二氧化碳以及自由和普遍存在的底物，有望成为可持续生物生产的最佳平台。选择移除的基因将通过计算方法和基因编辑技术进行识别。基因移除是在不影响生物体生长速度的情况下完成的。该项目在不同的合作项目下培训几名国内和国际本科生，学习分子工具的设计和实施，相关的计算技术和光合作用生物体的生理学。此外，该项目旨在与各种科学创业项目保持一致。该项目将聚球藻2973，一种显示出迄今观察到的最快光自养生长的蓝藻，通过在实验分析和代谢建模的指导下，通过多步骤简化其基因组的过程，将其开发成理想的底盘菌株，其中包括最先进的基因组编辑技术。通过插件报告通路的生长速度和生产力来评估减少的效果。在保持快速增长的同时最大限度地减少基因组，减轻了菌株的新陈代谢负担，消除了挑战可预测工程的神秘调控过程，并提高了对这一强大的自养主力的理解和控制。该奖项由分子和细胞生物科学部门的系统和合成生物学集群以及化学、生物工程、环境和运输系统部门的细胞和生化工程项目共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为是值得支持的。

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.