p -Coumaric acid is a critical building block for pharmaceuticals, cosmetics, and functional foods. While microbial production platforms typically rely on sugar feedstocks, this research leverages C. necator H16’s ability to use H 2 as an energy source and CO 2 as its sole carbon source. The research team, led by Prof. Xiaochun Qin at the University of Jinan, systematically redesigned the microbe’s metabolic network to channel carbon flux toward aromatic biosynthesis.
The engineering process involved selecting a tyrosine-derived pathway using tyrosine ammonia-lyase (TAL), which proved far more efficient in this host than a phenylalanine-based route. To overcome bottlenecks in the shikimate pathway, the team overexpressed key endogenous genes, including aroG1 , aroC , and aroQ1 . They also strategically replaced the native pheA gene with Escherichia coli ’s tyrA to redirect metabolic flux away from competing byproducts and toward p -CA. Additionally, introducing E. coli ’s pyridine nucleotide transhydrogenase ( pntAB ) boosted NADPH availability, while optimizing the nitrogen source with urea significantly enhanced titers.
These modifications resulted in an engineered strain, CNPCA39, that produced 25.4 mg/L of p -CA from fructose—a 1,593.3% increase over the initial strain. Crucially, under autotrophic conditions using a gas mixture of CO 2 , H 2 , and O 2 , the strain achieved de novo synthesis of p -CA, reaching a titer of 3.1 mg/L.
While the current autotrophic titer is modest compared to heterotrophic systems, the study establishes a foundational framework for CO 2 -based biomanufacturing. Future work will focus on blocking the microbe’s native p -CA degradation pathways and improving gas-liquid mass transfer to boost yields. This breakthrough paves the way for producing a wide array of phenylpropanoids—such as resveratrol and flavonoids—directly from industrial CO 2 emissions, supporting the transition to a circular bioeconomy.
The work entitled “ De novo synthesis of p -coumaric acid from fructose and carbon dioxide in chemoautotrophic Cupriavidus necator H16 ” was published in Systems Microbiology and Biomanufacturing (published on June 8, 2026).
Systems Microbiology and Biomanufacturing
Experimental study
Not applicable
De novo synthesis of p-coumaric acid from fructose and carbon dioxide in chemoautotrophic Cupriavidus necator H16
8-Jun-2026