Succinic Acid Production via Microbial Fermentation

Succinic acid is a four-carbon dicarboxylic acid that serves as a platform chemical for polymers, solvents, food additives and pharmaceutical precursors. Microbial fermentation offers a sustainable route to this compound by converting renewable biomass, such as glucose, glycerol or lignocellulosic hydrolysates, into succinic acid under controlled reactor conditions. Central to many processes is the engineering of metabolic pathways to channel carbon flux towards succinate rather than to competing by-products. Two principal biosynthetic routes are employed: the reductive tricarboxylic acid (rTCA) cycle, which fixes CO2 and yields succinate directly, and alternative bypasses such as the glyoxylate shunt. Strain improvement techniques—including heterologous enzyme expression, gene deletions to eliminate by-product formation, optimisation of cofactor balance (notably NADH regeneration) and adaptive laboratory evolution—have driven titers above 100 g/L in bench- and pilot-scale fermentations. Process formats vary from batch and fed-batch modes to continuous or biofilm reactors, each offering distinct advantages in productivity, yield and operational stability. Control of pH, CO2 supply and downstream recovery remains critical to economic viability. As biorefineries seek to integrate succinic acid production with biofuel or waste valorisation streams, advances in feedstock flexibility, reactor design and purification promise to position bio-based succinate as a competitive alternative to petrochemical routes.

Research from Nature Portfolio

Recent studies have demonstrated the power of pathway reconfiguration and enzyme optimisation to boost succinic acid biosynthesis. In one effort, a strictly aerobic yeast was engineered to host the rTCA cycle in its cytosol and mitochondria. Disruption of succinate dehydrogenase arrested growth, but adaptive laboratory evolution restored fitness and enabled NADH-coupled operation of oxidative and reductive loops. In pilot-scale fed-batch trials, this strain attained 111.9 g/L succinic acid at a yield of 0.79 g/g glucose in 62 hours. In parallel, structural and biochemical comparison of malate dehydrogenases (MDHs) from different bacteria identified an enzyme variant with high activity and low substrate inhibition. Incorporation of this optimised MDH into a succinate-producing bacterium resulted in a fed-batch productivity of 21.3 g/L·h and final titres exceeding 134 g/L, underscoring the importance of targeted enzyme selection in strain development.

Succinic Acid Production via Microbial Fermentation publication trend

The graph below shows the total number of articles in succinic acid production via microbial fermentation across all publications each year (not limited to Nature Index journals).

Technical terms

Reductive tricarboxylic acid (rTCA) cycle: A metabolic pathway running in reverse to the oxidative TCA cycle, fixing CO2 and generating succinic acid under microaerobic or anaerobic conditions.

Adaptive laboratory evolution (ALE): A technique for improving microbial performance by serially culturing cells under selective pressures to accumulate beneficial mutations.

Malate dehydrogenase (MDH): An enzyme catalysing the reversible conversion of malate to oxaloacetate, a key step in succinic acid biosynthesis.

Fed-batch fermentation: A cultivation mode in which nutrients are added incrementally to maintain optimal growth and product formation without complete nutrient exhaustion.

Platform chemical: A versatile intermediate molecule that can be transformed into a range of higher-value products, such as polymers, solvents and pharmaceuticals.

References

1. Reconfiguration of the reductive TCA cycle enables high-level succinic acid production by Yarrowia lipolytica. Nature Communications (2023).
2. Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase. Nature Communications (2020).
3. Biosynthetic Pathway and Metabolic Engineering of Succinic Acid. Frontiers in Bioengineering and Biotechnology (2022).
4. Evaluation of organic fractions of municipal solid waste as renewable feedstock for succinic acid production. Biotechnology for Biofuels and Bioproducts (2020).
5. Succinic Acid: Technology Development and Commercialization. Fermentation (2017).