<p>The direct reduction of CO<sub>2</sub> into one-carbon molecules is key to highly efficient biological CO<sub>2</sub>-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<sub>2</sub> to formate at aerobic conditions and ambient CO<sub>2</sub> 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 <i>E. coli</i> by supplementing C1-metabolism and serine biosynthesis from CO<sub>2</sub>. 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<sub>2</sub> fixation processes such as photosynthesis, and opening avenues for synthetic autotrophy.</p>

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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 N. Smith,
  • Virginie Pellouin,
  • Henrik M. Petri,
  • Vittorio Rainaldi,
  • Maren Nattermann,
  • Simon Burgener,
  • Nicole Paczia,
  • Jan Zarzycki,
  • Matthias Heinemann,
  • Arren Bar-Even,
  • Tobias J. Erb

摘要

The direct reduction of CO2 into one-carbon molecules is key to highly efficient biological CO2-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 CO2 to formate at aerobic conditions and ambient CO2 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 CO2. 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 CO2 fixation processes such as photosynthesis, and opening avenues for synthetic autotrophy.