The living world is largely divided into autotrophs that convert CO2 into biomass and heterotrophs that consume organic compounds. In spite of wide-spread interest in renewable energy storage and more sustainable food production, the engineering of industrially relevant heterotrophic model organisms to use CO2 as their sole carbon source has so far remained an outstanding challenge. I will describe the achievement of this transformation on laboratory timescales with the help of rational design making use of constraint-based modeling. We constructed and evolved Escherichia coli to produce all its biomass carbon from CO2. Reducing power and energy, but not carbon, are supplied via the one-carbon molecule formate, which can be produced electrochemically. Rubisco and phosphoribulokinase were co-expressed with formate dehydrogenase to enable CO2 fixation and reduction via the Calvin-Benson-Bassham cycle. Autotrophic growth was achieved following several months of continuous laboratory evolution in a chemostat under intensifying organic carbon limitation and confirmed via isotopic labeling.
Professor Ron Milo earned a BSc in Physics and Mathematics at the Hebrew University of Jerusalem and a PhD in Biological Physics at the Weizmann Institute of Science. He was the first fellow in Systems Biology at Harvard Medical School before joining the Department of Plant & Environmental Sciences at the Weizmann Institute.
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