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Journal Article

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

MPS-Authors
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McLean,  Richard
Understanding and Building Metabolism, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Schwander,  Thomas
Understanding and Building Metabolism, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Diehl,  Christoph
Understanding and Building Metabolism, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Cortina,  Nina Socorro
Understanding and Building Metabolism, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Paczia,  Nicole       
Core Facility Metabolomics and small Molecules Mass Spectrometry, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Zarzycki,  Jan
Understanding and Building Metabolism, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Erb,  Tobias J.       
Understanding and Building Metabolism, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

External Resource

https://doi.org/10.1126/sciadv.adh4299
(Publisher version)

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Citation

McLean, R., Schwander, T., Diehl, C., Cortina, N. S., Paczia, N., Zarzycki, J., et al. (2023). Exploring alternative pathways for the in vitro establishment of the HOPAC cycle for synthetic CO2 fixation. Science Advances, 9(24): eadh4299. doi:10.1126/sciadv.adh4299.


Cite as: https://hdl.handle.net/21.11116/0000-000D-4F77-6
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. Version 4.0 of the HOPAC cycle encompasses 11 enzymes from six different organisms, converting ~3.0 mM CO2 into glycolate within 2 hours. Our work moves the hypothetical HOPAC cycle from a theoretical design into an established in vitro system that forms the basis for different potential applications. Natural CO2-fixation pathways are expanded by a human-made alternative.