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

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

SUBMITTER: Schulz-Mirbach H 

PROVIDER: S-EPMC11599936 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature