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不断增加所造成的全球变暖威胁是两大挑战。将二氧化碳转化为食品或饲料似乎是同时应对这两个挑战的一个有希望的途径。与必须提供有机底物才能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自然自养二氧化碳固定途径。主要途径是Calvin-Benson-Bassham循环(CBB)，也称为还原戊糖磷酸循环。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自然宿主的碳固定，还是通过将其引入新的宿主。天然自养生物的问题是，缺乏针对这些生物的高效和可扩展的基因工具，而且它们很难在工业生物过程的规模上处理。虽然已经有一些光养蓝藻和化石菌的遗传方法，但我们在生物反应器中设计和培养这些生物(特别是光养蓝藻)的能力与异养平台生物如革兰氏阴性菌大肠杆菌和酵母酿酒酵母相比仍然是有限的。在这个项目中，我们将使用人工合成的自养大肠杆菌菌株来从二氧化碳中生产氨基酸。在这个项目中，我们将使用合成的自养大肠杆菌菌株来生产氨基酸。魏茨曼研究所罗恩·米洛教授的课题组研制出了自养型大肠杆菌，德国Tübingen大学的汉尼斯·林克教授的课题组研制出了用于生产氨基酸的异养型大肠杆菌。这两个小组在细菌新陈代谢的分析和建模方面都有专业知识，这将使我们能够改善合成的自养大肠杆菌菌株的新陈代谢，并优化它们以生产氨基酸。

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.