Arginine Metabolism: Enzymology, Nutrition, and Clinical Significance Production of Arginine by Fermentation

Studies on the production of L-arginine by fermentation using mutants of Corynebacterium (Brevibacterium), Bacillus, and Serratia have been conducted since the 1960s. More recently, the breeding of L-arginine production strains by gene recombination techniques using Escherichia coli has been investigated. To produce L-arginine efficiently by fermentation, it is necessary to breed strains with a strong biosynthetic pathway to L-arginine. Because L-arginine is biosynthesized from the precursor L-glutamic acid through ornithine and citrulline, the use of strains with a high capability for producing L-glutamic acid is desirable. Corynebacterium (Brevibacterium), which is well known in the production of L-glutamic acid, was selected as a starting strain for the breeding of an L-arginine producer and has been used on a commercial scale. Regarding the fermentation conditions, as for other amino acids, L-arginine fermentation is controlled by regulating pH near the neutral point. Due to its high oxygen requirement, L-arginine production is seriously impaired without sufficient oxygen. Advanced purification methods are necessary to obtain highly pure L-arginine from the fermentation broth. After fermentation is complete, bacterial cells and proteins are removed by means of a membrane or centrifugation, and impurities are removed by means of an ion-exchange resin or activated carbon. Highly pure L-arginine crystals can be obtained through concentration at the end of the process. J. Nutr. 134: 2854S–2857S, 2004.