Oxygenic photosynthesis evolved about 2.7 billion years ago among cyanobacteria in a CO₂ rich environment virtually free of O₂. This invention resulted in the development of the entire plant kingdom, which supplies organic carbon sources (as well as oxygen) for almost all heterotrophic organisms including humans. However, it turned out that photosynthetic CO₂ fixation is often limited by the available atmospheric CO₂ despite long-term process optimization. It has been discussed that natural evolution is constrained by the available parts in the biosphere, i.e. at a certain point innovation using entire new combinations are not possible anymore.

The newly appearing field of synthetic biology aims to overcome the constraints of natural evolution. In silico model approaches permit the free combination of all possible reactions in thermodynamically feasible pathways even including enzymatic reactions that have not been developed during natural evolution (Erb et al. 2017). In the field of CO₂ fixation, many thermodynamically better suited carboxylating enzymes exist compared to RubisCO that is used in plants. Hence, the design of new CO₂ fixation routes and their implementation into crop plants may optimize growth and yield under present environmental conditions (Weber and Bar-Even 2019). For example, formate dehydrogenases can incorporate CO₂ into the simplest organic compound formate, which can then be introduced into natural metabolism to supplement the Calvin-cycle. Such formate assimilation routes have been designed and successively proven in the model bacterium Escherichia coli (Trudeau et al. 2018). In our cooperative projects (BMBF and EU), we aim to establish such routes in the cyanobacterial model to test if the designed pathways are compatible with photoautotrophic growth and really improve overall CO₂ assimilation thereby reducing the negative impact of photorespiratory 2PG metabolism.

Erb TJ, Jones PR, Bar-Even A (2017) Synthetic metabolism: metabolic engineering meets enzyme design. Current Opinion in Chemical Biology 37:56-62

Trudeau DL, Edlich-Muth C, Zarzycki J, Scheffen M, Goldsmith M, Khersonsky O, Avizemer Z, Fleishman SJ, Cotton CAR, Erb TJ, Tawfik DS, Bar-Even A (2018) Design and in vitro realization of carbon-conserving photorespiration. Proceeding of the National Academy of Sciences USA 115:E11455-E11464.

Weber APM, Bar-Even A (2017) Update: Improving the efficiency of photosynthetic carbon reactions. Plant Physiology 179:803-812