Metabolic Engineering for Itaconic Acid Production

The biochemical pathways leading to the formation and degradation of itaconic acid are known to some extent, and the current knowledge is used to improve 

It is speculated that the situation is similar for itaconic acid production with A. terreus. 

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 

However, the cadA gene was also introduced into other organisms, and it was possible to produce itaconic acid in organisms such as E. coli, S. cerevisiae, Yarrowia lipolytica, Candida lignohabitans, Synechocystis sp., and Corynebac-terium glutamicum. The respective studies with the different host organisms and the achieved itaconic acid titers are listed in Table 15.1. 

One approach to enhance itaconic acid production is to provide more substrate for the CAD enzyme by either blocking the TCA cycle at the level of isocitrate or pushing the formation of cz s-aconitate. Consequently, CadA was expressed in a hied (isocitrate dehydrogenase) strain along with an overexpression of aconitase 

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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. 

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