Biotechnological Production of Itaconic Acid

Itaconic acid is a C5 unsaturated dicarboxylic acid of growing industrial importance, serving as a versatile platform chemical for polymers, resins, coatings and speciality fibres. Biotechnological production is predominantly achieved through microbial fermentation, exploiting the natural capacity of fungi such as Aspergillus terreus and Ustilago maydis, as well as engineered bacterial hosts. Central to the process is the decarboxylation of cis-aconitate—a tricarboxylic acid (TCA) cycle intermediate—catalysed by cis-aconitate decarboxylase, yielding itaconate with high stereospecificity. Production regimes vary from traditional batch cultivations to optimised fed-batch and continuous processes, incorporating advanced bioreactor configurations and in situ product removal to alleviate product inhibition and enhance overall titres. Feedstocks have evolved from pure sugars to lignocellulosic hydrolysates and industrial by-products such as crude glycerol and molasses, reducing production costs and improving sustainability profiles. Genetic and metabolic engineering strategies have targeted pathway enzymes, transporters, redox balancing and regulatory circuits, enabling dramatic improvements in yield, productivity and robustness. These innovations underpin the shift towards a circular bioeconomy, where itaconic acid represents a renewable alternative to petrochemically derived acrylates, supporting applications in biodegradable plastics, medical hydrogels and water-treatment materials.

Research from Nature Portfolio

Whole-cell bioconversion systems have emerged as a rapid alternative to conventional fermentation. A recent study demonstrated the conversion of citrate to itaconate in Escherichia coli by co-expressing multiple copies of the cis-aconitate decarboxylase gene and enhancing aconitase activity. Operating without external buffering agents, this approach achieved conversion yields above 60% and productivities exceeding 2 g L⁻¹ h⁻¹, generating over 40 g L⁻¹ itaconate in under 24 h. The streamlined bioconversion reduces downstream processing and by-product formation, offering a cost-effective route to high-grade itaconate from citrate feedstocks.

Biotechnological Production of Itaconic Acid publication trend

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

Technical terms

cis-Aconitate Decarboxylase: Enzyme that catalyses the decarboxylation of cis-aconitate to produce itaconic acid.

Fed-batch Fermentation: Cultivation mode in which substrates are incrementally added to maintain optimal growth and production rates.

Yield: Mass of product obtained per mass of substrate consumed, expressed as g product g⁻¹ substrate.

Productivity: Rate of product formation over time in a bioprocess, typically given as g L⁻¹ h⁻¹.

Platform Chemical: Base molecule used as a precursor for synthesising a range of downstream materials and speciality chemicals.

References

1. Itaconate Production from Crude Substrates with U. maydis: Scale-up of an Industrially Relevant Bioprocess. Microbial Cell Factories (2024).
2. Production of itaconate by whole-cell bioconversion of citrate mediated by expression of multiple cis-aconitate decarboxylase (cadA) genes in Escherichia coli. Scientific Reports (2017).
3. Integrated strain- and process design enable production of 220 g L−1 itaconic acid with Ustilago maydis. Biotechnology for Biofuels and Bioproducts (2019).