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

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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.