Formate-driven in situ CO₂ recycling for efficient succinic acid bioproduction in engineered Actinobacillus succinogenes.
- 1MOE Key Laboratoy of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, No. 2 Linggong Road, Ganjingzi District, Dalian, 116024, Liaoning, People's Republic of China.
- 2MOE Key Laboratoy of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, No. 2 Linggong Road, Ganjingzi District, Dalian, 116024, Liaoning, People's Republic of China. [email protected].
Abstract
Background
Succinic acid (SA) biosynthesis presents a promising sustainable alternative to petrochemical routes, yet industrial potential is often hampered by inefficient CO₂ fixation and redox imbalances.Results
To systematically address these bottlenecks, a synergistic metabolic engineering strategy was developed in Actinobacillus succinogenes by co-expressing the endogenous gene of formate dehydrogenase (FdoG) and the heterologous gene of phosphoenolpyruvate carboxylase (PPC). This design established a self-reinforcing metabolic loop where FdoG-mediated formate oxidation generated in situ CO₂ and NADH, which were immediately channeled into the PPC-driven carboxylation pathway. Physiological characterizations, utilizing real-time off-gas analysis, demonstrated that this pathway effectively functions as an endogenous CO₂ generator, decoupling production from external mass transfer limitations. Furthermore, carbon flux distribution analysis confirmed the synergistic efficacy, revealing a 12.11% increase in succinate-directed flux and a significant reduction in byproduct accumulation compared to the wild type. To fully exploit this formate-utilization potential, an optimized fed-batch fermentation with pulsed formate feeding was implemented. Consequently, the engineered strain AS-PF achieved a remarkable succinate titer of 96.64 g/L, with a productivity of 1.38 g/ (L·h), corresponding to an overall product yield of 0.78 g/g based on the total consumed mixed carbon source (glucose and formate).Conclusion
This study establishes a sustainable and efficient platform for SA bioproduction by synergistically integrating formate metabolism-driven CO₂ recycling with enhanced biosynthetic pathways, thereby advancing the valorization of C1 compounds.
Related
- High-Entropy Alloy-Engineered ZnIn2S4 Photocatalyst for Efficient In Vitro Eradication of MRSA and Inhibition of Biofilm Formation via ROS-Mediated Mechanisms
- Strain engineering of Aspergillus species for industrial enzymes bioproduction: a comprehensive review.
- Biological process engineering by Pseudomonas sp. ABC1: a discovery-stage ecological chassis for open bioproduction
- An Integrated Self-Powered Photoelectrocatalytic System for Quadruple-Function Water Remediation: Organic Degradation, Radionuclide Recycling, Energy Recovery, and Toxicity Evaluation.
- Iron and manganese recycling in the Southern Ocean: the relative influence of the “ferrous wheel” and the “spinning manga”
BibTeX
@article{zhao2026formatedriven,
title = {{Formate-driven in situ CO₂ recycling for efficient succinic acid bioproduction in engineered Actinobacillus succinogenes.}},
author = {Mingyang Zhao and Li Wang and Yuanming Ye and Yaqin Sun and Zhilong Xiu},
journal = {Biotechnology for biofuels and bioproducts},
year = {2026},
month = jul,
doi = {10.1186/s13068-026-02799-7},
url = {https://europepmc.org/article/MED/42902297},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Formate-driven in situ CO₂ recycling for efficient succinic acid bioproduction in engineered Actinobacillus succinogenes.
AU - Mingyang Zhao
AU - Li Wang
AU - Yuanming Ye
AU - Yaqin Sun
AU - Zhilong Xiu
PY - 2026
DA - 2026/07/01
JO - Biotechnology for biofuels and bioproducts
DO - 10.1186/s13068-026-02799-7
UR - https://europepmc.org/article/MED/42902297
AB - Background Succinic acid (SA) biosynthesis presents a promising sustainable alternative to petrochemical routes, yet industrial potential is often hampered by inefficient CO₂ fixation and redox imbalances.Results To systematically address these bottlenecks, a synergistic metabolic engineering strategy was developed in Actinobacillus succinogenes by co-expressing the endogenous gene of formate dehydrogenase (FdoG) and the heterologous gene of phosphoenolpyruvate carboxylase (PPC). This design established a self-reinforcing metabolic loop where FdoG-mediated formate oxidation generated in situ CO₂ and NADH, which were immediately channeled into the PPC-driven carboxylation pathway. Physiological characterizations, utilizing real-time off-gas analysis, demonstrated that this pathway effectively functions as an endogenous CO₂ generator, decoupling production from external mass transfer limitations. Furthermore, carbon flux distribution analysis confirmed the synergistic efficacy, revealing a 12.11% increase in succinate-directed flux and a significant reduction in byproduct accumulation compared to the wild type. To fully exploit this formate-utilization potential, an optimized fed-batch fermentation with pulsed formate feeding was implemented. Consequently, the engineered strain AS-PF achieved a remarkable succinate titer of 96.64 g/L, with a productivity of 1.38 g/ (L·h), corresponding to an overall product yield of 0.78 g/g based on the total consumed mixed carbon source (glucose and formate).Conclusion This study establishes a sustainable and efficient platform for SA bioproduction by synergistically integrating formate metabolism-driven CO₂ recycling with enhanced biosynthetic pathways, thereby advancing the valorization of C1 compounds.
SN - 2731-3654
ER -