Exploring alternative pathways for the in vitro establishment of the HOPAC cycle for synthetic CO₂ fixation.

ABSTRACT: Nature has evolved eight different pathways for the capture and conversion of CO₂, including the Calvin-Benson-Bassham cycle of photosynthesis. Yet, these pathways underlie constrains and only represent a fraction of the thousands of theoretically possible solutions. To overcome the limitations of natural evolution, we introduce the HydrOxyPropionyl-CoA/Acrylyl-CoA (HOPAC) cycle, a new-to-nature CO₂-fixation pathway that was designed through metabolic retrosynthesis around the reductive carboxylation of acrylyl-CoA, a highly efficient principle of CO₂ fixation. We realized the HOPAC cycle in a step-wise fashion and used rational engineering approaches and machine learning-guided workflows to further optimize its output by more than one order of magnitude. V

SUBMITTER: McLean R 

PROVIDER: S-EPMC10266731 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature