Itaconic acid

Itaconic acid, or methylidenesuccinic acid, is an organic compound. This dicarboxylic acid is a white solid that is soluble in water, ethanol, and acetone. Historically, itaconic acid was obtained by the distillation of citric acid, but currently it is produced by fermentation. The name itaconic acid was devised as an anagram of aconitic acid, another derivative of citric acid. Itaconic acid, or methylidenesuccinic acid, is an organic compound. This dicarboxylic acid is a white solid that is soluble in water, ethanol, and acetone. Historically, itaconic acid was obtained by the distillation of citric acid, but currently it is produced by fermentation. The name itaconic acid was devised as an anagram of aconitic acid, another derivative of citric acid. Since the 1960s, it is produced industrially by the fermentation of carbohydrates such as glucose or molasses using fungi such as Aspergillus itaconicus or Aspergillus terreus. For A. terreus the itaconate pathway is mostly elucidated. The generally accepted route for itaconate is via glycolysis, tricarboxylic acid cycle, and a decarboxylation of cis-aconitate to itaconate via cis-aconitate-decarboxylase. The smut fungus Ustilago maydis uses an alternative route. Cis-aconitate is converted to the thermodynamically favoured trans-aconitate via aconitate-Δ-isomerase (Adi1). trans-Aconitate is further decarboxylated to itaconate by trans-aconitate-decarboxylase (Tad1). Itaconic acid is also produced in cells of macrophage lineage and as such it has in vitro activity against bacteria expressing the enzyme isocitrate lyase such as Salmonella enterica and Mycobacterium tuberculosis. However, cells of macrophage lineage have to 'pay the price' for making itaconate, and they lose the ability to perform mitochondrial substrate-level phosphorylation. Dry distillation of citric acid affords itaconic anhydride, which undergoes hydrolysis to itaconic acid. Upon heating, itaconic anhydride isomerizes to citraconic acid anhydride, which can be hydrolyzed to citraconic acid (2-methylmaleic acid). Partial hydrogenation of itaconic acid over Raney nickel affords 2-methylsuccinic acid.