3. Synthetic biology attempts for new CO2-related pathways

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.

Work flow in our cooperative projects aiming to stepwise establish new CO2 fixation routes into plants to reduce the negative impact of photorespiratory 2-PG 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