Itaconic acid enzymes

Levinson, W.E., Kurtzman, C.P. and Kuo, T.M. 2006. Production of Itaconic Acid by Pseudozyma Antarctica NRRL Y-7808 Under Nitrogen-Limited Growth Conditions. Enzyme Microb. Technol., 39, 824-827. 

There are many organic acids that can be produced by microbial or biochemical means. However, at present, only acetic acid (as vinegar), citric acid, itaconic acid, gluconic acid, 2-keto-gulonic acid, and lactic acid are produced industrially by fermentation. Other organic acids, such as fumaric, gallic, malic, and tartaric acids, once produced by fermentation or enzyme processes, are now produced commercially, predominantly by the more economic means of chemical synthesis. 

Genes and Enzymes Involved In the Biosynthesis of Itaconic Acid in A. terreus... 

Itaconic acid is a derivative of TCA cycle intermediates. Although all main genes responsible for glycolysis and citrate production have been known for decades, it took some time until the gene responsible for the CAD activity was identified. In 2002, the enzyme was purified for the first time, its value for cis-aconitate was determined to be 2.45 mM (pH 6.2, 37 °C), and it was shown to be sensitive... 

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... 

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. 

Pharmaceuticals are only a part of natural products derived from filamentous organisms. Filamentous fungi are also grown industrially for the production of natural products other than pharmaceuticals. Organic acids such as citric, itaconic and gluconic acids, carotenoids, taste and aroma compounds, and a variety of industrial enzymes such as amylases, lipases, dextranases and proteases are also extracted from these fungi. 

In 1995, Bonnarme et al. [110] used the analytical techniques that combine isotopic tracing, nuclear magnetic resonance spectroscopy, and mass spectroscopy to compare the enzyme systems of intact cells of high- and low-producing strains of A. terreus. Results show that itaconate formation requires de novo protein synthesis. During acid formation, TCA cycle intermediates increase in both strains. Furthermore, data showed that both the BMP pathway and the TCA cycle are involved in itaconate biosynthesis. Based on the biosynthetic pathway (Fig. 15), one itaconate molecule is produced from one hexose molecule with a theoretical weight yield of 72.2%. The actual yield should be lower due to the loss of carbon to biomass accumulation and cell maintenance. 

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