Metabolic itaconic acid

Previously, itaconic acid was isolated from pyrolytic products of citric acid or produced by converting aconitic acid present in sugar cane juice. It is now produced on a commercial basis predominantly by direct fermentation of sugars. The biosynthesis of itaconic acid follows the metabolic sequence shown in Figure 30.15. 

Fig. 30.15. Proposed metabolic sequence for biosynthesis of itaconic acid.

For A. niger, it was shown that especially aconitase activity has a significant impact on itaconic acid production. In this context, it is necessary to consider the locahzation of the metabolic pathways [60]. Citric acid is synthesized in the mitochondria of A terreus, and aconitase activity is also mainly found in this compartment, whereas CAD is found in the cytosol. For A. niger, the same situation applies [61], and when expressing CadA in this organism, it is also localized in the cytosol. Re-targeting of either aconitase or CAD activity in A. niger had a... 

In the last few years, substantial progress has been made in the understanding of the biochemical mechanisms leading to the formation of itaconic acid. Today, the itaconic acid metabolic pathway can be transferred to different microbial hosts. However, still the titers obtained in the native production hosts are not reached by any other system. This implies that further insights into the production mechanisms will be necessary to fully understand the itaconic acid biochemistry in A. terreus and to be able to transfer it also to other systems. Only when it is possible to build such a system in a rational manner will it be fair to say that the synthesis is sufficiently understood. 

J., Pailot, A. et al. (2013) Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc. Natl. Acad. Sci. U.S.A., 110, 7820-7825. 

Xhe metabolism of itaconic acid by liver mitochondria. J. Biol. Chem.,... 

Blumhoff, M.L., Steiger, M.G., Mattanovich, D., and Sauer, M. (2013) Targeting enzymes to the right compartment metabolic engineering for itaconic acid production by Aspergillus niger. Metah. Eng., 19C, 26-32. 

Aso, Y. et al (2014) Production of itaconic acid using metabolically engineered Escherichia coli. /. Gen. Appl Microbiol, 60, 191-197. 

J. et al. (2014) Metabolic engineering of Saccharomyces cerevisiae for itaconic acid production. Appl Microbiol. Biotechnol, 98, 8155-8164. 

A. et al (2015) Metabolic Engineering of Yarrowia lipolytica for itaconic acid production. Metab. Eng., 32, 66-73. 

The biosynthesis of itaconic acid once was believed to follow the decarboxylation of aconitic acid of the citric acid cycle. Now it is thought to follow the metabolic sequence shown in Fig. 24.19. 

Vuoristo, K.S., Mars, A.E., Sangra, J.V., Springer, J. et al. (2015) Metabolic engineering of the mixed-acid fermentation pathway of Escherichia coli for anaerobic production of glutamate and itaconate. AAIB Express, 5, 61. 

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