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Exceeding Conventional Maximum Carbon Yields via Heterotrophic CO2 Fixation

ABSTRACT: Maximizing carbon yields is crucial in the microbial production of diverse biochemicals. However, microorganisms, particularly heterotrophs, release carbon dioxide (CO2) during the oxidation of organic compounds for energy and building blocks. This metabolism limits the theoretical maximum carbon yield and constrains the development of efficient microbial cell factories. Specifically, metabolite production from tricarboxylic acid (TCA)-cycle intermediates involves major CO2 emission steps, leading to unavoidable carbon loss. In the present study, the metabolic pathway in Escherichia coli, a model heterotroph, was synthetically rewired to facilitate CO2 fixation and maximize carbon yields. Specifically, we blocked multiple routes to prevent pyruvate oxidation to acetyl-CoA, which was identified as a major CO2 emission step, and promoted CO2 incorporation into TCA cycle intermediates by reengineering endogenous pathways. This strategy was applied to produce itaconate, a promising bioplastic precursor, achieving a notable itaconate yield of 0.86 C mol/C substrate mol, exceeding the conventional maximum carbon yield of 0.83 C mol/C mol. This heterotrophic CO2 fixation strategy can be used to produce TCA-derived chemicals and enhance the economic viability of microbial production.

ORGANISM(S): Escherichia coli W

PROVIDER: GSE315248 | GEO | 2026/06/18

REPOSITORIES: GEO

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