Background: Itaconic acid is a C5 dicaboxylic acid that can serve as a building block to be used in industry
to synthesize polymers that are currently based on petroleum-based components.
Methods: An overview of the recent literature on microbial itaconic acid production is given in this minireview.
The biosynthetic pathways as they are known in Aspergillus terreus and Ustilago maydis are described.
Major advances have been made in the development of different microorganisms to serve as potential
novel itaconic acid production hosts. Although fermentation strategies are discussed, our main focus is
therefore on metabolic engineering strategies for optimal itaconic acid biosynthesis.
Results: Itaconic acid is naturally produced by Aspergillus terreus, certain Ustilago and Candida species and
Pseudozyma antarctica. Also in mammalian cells itaconic acid is found during macrophage activation. The
biosynthetic pathway in A. terreus was well studied and the crucial enzyme for itaconic acid synthesis was
found to be cis-aconitate decarboxylase (CadA) that converts cis-aconitate into itaconate. On one hand, optimization
of itaconic acid production was done by optimizing fermentation processes and by applying metabolic
engineering strategies to the natural producers, most of this was done with A. terreus. On the other
hand, the identification of CadA allowed the exploration of heterologous expression of the gene in different
hosts. Since citric acid is the metabolic precursor for itaconic acid biosynthesis, many research efforts have
focused on Aspergillus niger as a potential itaconic acid producer. The results of this research showed that
besides the heterologous expression of cadA, transport between different compartments and re-routing of the
central carbon metabolism are important factors for the efficient biosynthesis of itaconic acid.
Conclusion: Several microorganisms have been investigated in the past years as potential itaconic acid producing
hosts. Titers obtained by metabolic engineering of non-producing hosts range between 14.5 mg/L
and 7.8 g/L. Although substantial progress has been made, the titers are not yet competitive with the titers
obtained with the natural producer A. terreus.