New-to-nature CO2-dependent acetyl-CoA assimilation enabled by an engineered B12-dependent acyl-CoA mutase

Helena Schulz-Mirbach, Philipp Wichmann, Ari Satanowski (), Helen Meusel, Tong Wu, Maren Nattermann, Simon Burgener, Nicole Paczia, Arren Bar-Even and Tobias J. Erb ()
Additional contact information
Helena Schulz-Mirbach: Max Planck Institute for Terrestrial Microbiology
Philipp Wichmann: Max Planck Institute for Terrestrial Microbiology
Ari Satanowski: Max Planck Institute for Terrestrial Microbiology
Helen Meusel: Max Planck Institute of Molecular Plant Physiology
Tong Wu: Max Planck Institute of Molecular Plant Physiology
Maren Nattermann: Max Planck Institute for Terrestrial Microbiology
Simon Burgener: Max Planck Institute for Terrestrial Microbiology
Nicole Paczia: Max Planck Institute for Terrestrial Microbiology
Arren Bar-Even: Max Planck Institute of Molecular Plant Physiology
Tobias J. Erb: Max Planck Institute for Terrestrial Microbiology

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Acetyl-CoA is a key metabolic intermediate and the product of various natural and synthetic one-carbon (C1) assimilation pathways. While an efficient conversion of acetyl-CoA into other central metabolites, such as pyruvate, is imperative for high biomass yields, available aerobic pathways typically release previously fixed carbon in the form of CO2. To overcome this loss of carbon, we develop a new-to-nature pathway, the Lcm module, in this study. The Lcm module provides a direct link between acetyl-CoA and pyruvate, is shorter than any other oxygen-tolerant route and notably fixes CO2, instead of releasing it. The Lcm module relies on the new-to-nature activity of a coenzyme B12-dependent mutase for the conversion of 3-hydroxypropionyl-CoA into lactyl-CoA. We demonstrate Lcm activity of the scaffold enzyme 2-hydroxyisobutyryl-CoA mutase from Bacillus massiliosenegalensis, and further improve catalytic efficiency 10-fold by combining in vivo targeted hypermutation and adaptive evolution in an engineered Escherichia coli selection strain. Finally, in a proof-of-principle, we demonstrate the complete Lcm module in vitro. Overall, our work demonstrates a synthetic CO2-incorporating acetyl-CoA assimilation route that expands the metabolic solution space of central carbon metabolism, providing options for synthetic biology and metabolic engineering.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53762-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53762-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53762-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().