By systematically integrating systems metabolic engineering strategies—such as synthetic biology, genome editing, and pathway optimization—the group significantly boosted production titers, yields, and product diversity.
Corynebacterium glutamicum, first identified in 1956 for its exceptional glutamic acid production, has since become a cornerstone microorganism in industrial biotechnology, particularly for manufacturing monosodium glutamate and other amino acids. Thanks to its metabolic versatility, safety profile, and capacity to utilize a wide range of substrates, C. glutamicum has emerged as a promising platform for constructing sustainable microbial cell factories. Recent advances in genetic and metabolic engineering have expanded its product range to include organic acids and terpenoids. However, challenges remain in optimizing its performance on non-conventional feedstocks such as lignocellulosic sugars and one-carbon compounds. These limitations highlight the need for innovative strategies to enhance substrate utilization, stress tolerance, and multifunctional cell factory design.
A study (DOI:10.1016/j.bidere.2025.100008) published in BioDesign Research on 26 February 2025 by Chen-Guang Liu’s team, Shanghai Jiao Tong University, opens avenues for more sustainable and cost-effective bio-based manufacturing of chemicals and materials, paving the way for industrial biorefineries that can reduce reliance on petrochemicals.
To explore the potential of Corynebacterium glutamicum as a robust microbial chassis for industrial biotechnology, researchers implemented a variety of metabolic engineering strategies to enable the utilization of non-model feedstocks, including lignocellulosic sugars, glycerol, methanol, and formic acid. They introduced and optimized key heterologous pathways and transport systems to allow efficient assimilation and conversion of pentose sugars such as xylose and arabinose—two major components of lignocellulosic biomass. For xylose, combinations of the xylose isomerase (XI) and Weimberg (WMB) pathways, including the expression of genes such as xylA, xylB, and the xylXABCD operon, were engineered into C. glutamicum, enabling growth on xylose as a sole carbon source. Transporter enhancements, like introducing xylE or araE, further improved sugar uptake. Similarly, arabinose assimilation was enabled via the araBAD operon from E. coli, leading to strains capable of producing organic acids and isobutanol from arabinose. For glycerol utilization, researchers expressed enzymes from E. coli, Klebsiella pneumoniae, and Citrobacter freundii to construct an active glycerol pathway, boosting growth rates and glycerol conversion efficiency. To harness one-carbon compounds, methanol assimilation was achieved by introducing methanol dehydrogenase (mdh) and key RuMP pathway enzymes, while formate assimilation relied on the reductive glycine pathway. Further, they developed strains with optimized flux control and cofactor regeneration systems to metabolize these C1 substrates effectively. These engineering strategies were validated through isotope tracing and fermentation assays, demonstrating the successful transformation of C. glutamicum into a multi-substrate platform. Collectively, these modifications significantly broadened the substrate scope and biochemical output of C. glutamicum, offering a foundation for producing diverse bio-based chemicals from renewable and low-cost resources.
This review summarizes recent advances in engineering Corynebacterium glutamicum into a versatile microbial cell factory for biochemical production. Originally used for amino acid synthesis, C. glutamicum has been reprogrammed to utilize non-conventional carbon sources such as xylose, arabinose, glycerol, methanol, and formic acid. It has also been optimized to produce various high-value compounds, including organic acids (e.g., lactate, succinate), amino acids (e.g., glutamate, lysine), and terpenoids (e.g., lycopene, pinene). The paper highlights challenges such as carbon catabolite repression and byproduct formation, suggesting that future improvements will rely on systems biology, multi-omics integration, and adaptive laboratory evolution.
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References
DOI
10.1016/j.bidere.2025.100008
Original Source URL
https://doi.org/10.1016/j.bidere.2025.100008
Funding information
This work was supported by the National Natural Science Foundation of China [22208212]; Startup Fund for Young Faculty at SJTU (SFYF at SJTU).
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