Metabolic engineering of autotrophic E. coli strains for biotechnological production of amino acids from CO2

养活不断增长的人口的需要和二氧化碳等温室气体增加造成的全球变暖的威胁是两大挑战。将二氧化碳转化为粮食或饲料似乎是同时应对这两个挑战的一个有希望的途径。与必须提供有机基质用于生长的异养生物不同，自养微生物直接从二氧化碳（CO2）产生生物质，并从光（光自养）或外部电子供体（化学自养）获得能量。我们知道自然界中存在六种不同的天然自养CO2固定途径。主要的途径是卡尔文-本森-巴斯沙姆循环（CBB），也称为还原性磷酸戊糖循环。CBB循环为工业应用提供了巨大的潜力，无论是通过改善藻类和细菌等天然宿主的碳固定，还是通过将其引入新的宿主。天然自养生物的问题是，这些生物缺乏有效和可扩展的遗传工具，并且难以在工业生物过程的规模上进行处理。虽然遗传方法存在一些光合蓝藻和化能无机营养菌，我们的能力，工程和培养这些生物（特别是光合蓝藻）在生物反应器中仍然是有限的异养平台生物，如革兰氏阴性细菌大肠杆菌和酵母酿酒酵母。E.大肠杆菌可以说是最有利的生产生物体，由于快速生长，高产量，成本效益和强大的处理在工业生物过程中。大肠杆菌菌株从二氧化碳中生产氨基酸。自养型E.罗恩米洛教授（魏茨曼研究所）的研究小组已经开发了大肠杆菌菌株，Hannes Link教授（蒂宾根大学）的研究小组已经开发了异养大肠杆菌。大肠杆菌菌株进行氨基酸生产。这两个小组都有分析和模拟细菌代谢的专业知识，这将使我们能够改善合成的自养E。大肠杆菌菌株，并优化它们用于生产氨基酸。

The need to feed the growing human population and the threat of global warming caused by increasing greenhouse gases such as CO2 are two major challenges. Converting CO2 into food or feed stocks seems to be a promising avenue to simultaneously address both of these challenges. Unlike heterotrophic organisms that must be supplied with organic substrates for growth, autotrophic microorganisms generate biomass directly from carbon dioxide (CO2) and derive energy from light (photoautotrophy) or an external electron donor (chemoautotrophy). We know of six different natural autotrophic CO2 fixation pathways that exist in nature. The predominant pathway is the Calvin-Benson-Bassham cycle (CBB) also known as the reductive pentose phosphate cycle. The CBB cycle offers a great potential for industrial applications, either by improving carbon fixation in natural hosts such as algae and bacteria, or by introducing it into new hosts. The problem with natural autotrophs is that efficient and scalable genetic tools for these organisms are missing, and they are difficult to handle at the scale of industrial bioprocesses. Although genetic methods exist for some phototrophic cyanobacteria and chemolithotrophs, our ability to engineer and culture these organisms (especially phototrophic cyanobacteria) in bioreactors is still limited compared to heterotrophic platform organisms such as the gram-negative bacterium Escherichia coli and the yeast Saccharomyces cerevisiae. E. coli is arguably the most favourable production organism due to rapid growth, high yields, cost effectiveness and robust handling in industrial bioprocesses.In this project, we will use synthetic autotrophic E. coli strains to produce amino acids from CO2. Autotrophic E. coli strains have been developed in the research group of Prof. Ron Milo (Weizmann Institute), and the research group of Prof. Hannes Link (University of Tübingen) has developed heterotrophic E. coli strains for amino acid production. Both groups have expertise with analysis and modelling of bacterial metabolism, which will enable us to improve metabolism of the synthetic autotrophic E. coli strains and optimize them for production of amino acids.