Design and implementation of aerobic and ambient CO2-reduction as an entry-point for enhanced carbon fixation
Ari Satanowski, Daniel G. Marchal, Alain Perret, Jean‐Louis Petit, Madeleine Bouzon, Volker Döring, Ivan Dubois, Hai He, Edward Smith, Virginie Pellouin, Henrik M. Petri, Vittorio Rainaldi, Maren Nattermann, Simon Burgener, Nicole Paczia, Jan Zarzycki, Matthias Heinemann, Arren Bar‐Even, Tobias J. Erb
Abstract
Abstract The direct reduction of CO 2 into one-carbon molecules is key to highly efficient biological CO 2 -fixation. However, this strategy is currently restricted to anaerobic organisms and low redox potentials. In this study, we introduce the CORE cycle, a synthetic metabolic pathway that converts CO 2 to formate at aerobic conditions and ambient CO 2 levels, using only NADPH as a reductant. Combining theoretical pathway design and analysis, enzyme bioprospecting and high-throughput screening, modular assembly and adaptive laboratory evolution, we realize the CORE cycle in vivo and demonstrate that the cycle supports growth of E. coli by supplementing C1-metabolism and serine biosynthesis from CO 2 . We further analyze the theoretical potential of the CORE cycle as a new entry-point for carbon in photorespiration and autotrophy. Overall, our work expands the solution space for biological carbon reduction, offering a promising approach to enhance CO 2 fixation processes such as photosynthesis, and opening avenues for synthetic autotrophy.