Fumaric Acid Production via Microbial Fermentation

Fumaric acid is a C4 dicarboxylic acid of high industrial value, serving as a food acidulant, pharmaceutical intermediate and monomer precursor. Microbial fermentation offers a sustainable alternative to petrochemical synthesis, harnessing the native metabolic pathways of fungi and yeasts. In particular, filamentous fungi such as Rhizopus oryzae and related species channel carbohydrate feedstocks through glycolysis into the tricarboxylic acid cycle, where fumarase catalyses the dehydration of malate to fumarate. Process parameters—including pH, oxygen supply, nutrient limitation and morphology—have a profound effect on yield, productivity and by-product formation. Advances in bioreactor design, feed-rate control and downstream separation are key to enhancing titre and purity. Integration of biorefineries with renewable biomass streams further underlines the global significance of biotech-based fumaric acid, aligning with circular economy and carbon neutrality goals.

Research from Nature Portfolio

Recent studies have demonstrated the selective recovery of fumaric acid from mixed fermentation broths by facilitated pertraction. A liquid-membrane system employing Amberlite LA-2 in n-heptane capitalises on differences in acidity and molecular size to enrich fumarate over malate and succinate. Control of pH gradients between feed and stripping phases, along with carrier concentration, enables a selectivity factor exceeding 18 under optimised conditions. Viscosity modulation further amplifies selectivity by hindering diffusion of larger diacids, improving downstream purification efficiency at industrial scale.

Research from all publishers

Transcriptomic profiling of Rhizopus delemar under varying pH conditions has elucidated the regulation of carbohydrate-active enzymes and key dehydrogenases. Optimal growth and enzyme activities were recorded at near-neutral pH, with over a thousand genes showing differential expression, informing future metabolic engineering efforts. An alternative in vitro approach has been developed through a cell-free multi-enzyme catalytic system that converts low-cost substrates acetate and glyoxylate into fumarate. By co-ordinating acetyl-CoA synthase, malate synthase and fumarase, the pathway achieved a 34 % conversion yield, demonstrating a modular route free from cellular maintenance demands. In a yeast-like system, engineering of the ornithine-urea cycle in Aureobasidium pullulans var. aubasidani enabled high-level fumarate biosynthesis. Deletion of non-essential pathways and overexpression of pyruvate carboxylase produced over 93 g L⁻¹ fumarate in fed-batch mode, fixing CO₂ and exemplifying a green, carbon-neutral process.

Fumaric Acid Production via Microbial Fermentation publication trend

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

Technical terms

Facilitated pertraction: A liquid-membrane separation method using a carrier and pH gradient to selectively extract target acids.

Cell-free multi-enzyme catalytic system: An in vitro assembly of purified enzymes that catalyses sequential reactions without living cells.

Ornithine-urea cycle (OUC): A metabolic pathway that converts nitrogenous compounds into urea, here linked to fumarate formation.

Transcriptomics: Genome-wide analysis of gene expression levels to understand metabolic responses under varying conditions.

References

1. Fumaric Acid Production: A Biorefinery Perspective. Fermentation (2018).
2. Selective pertraction of dicarboxylic acids from simulated Rhizopus oryzae fermentation broths. Scientific Reports (2023).
3. Transcriptomic analysis and carbohydrate metabolism-related enzyme expression across different pH values in Rhizopus delemar. Frontiers in Microbiology (2024).
4. Conversion of acetate and glyoxylate to fumarate by a cell-free synthetic enzymatic biosystem. Synthetic and Systems Biotechnology (2023).
5. The ornithine-urea cycle involves fumaric acid biosynthesis in Aureobasidium pullulans var. aubasidani, a green and eco-friendly process for fumaric acid production. Synthetic and Systems Biotechnology (2022).