Actuality and prospect of L-malci acid

L-malic acid is a ubiquitous dicarboxylic acid found in all organisms, but its name derives from the fact that it was first isolated from unripe apples in 1785. In 1967, it was classified as a safe food-grade product by the U.S. Food and Drug Administration (FDA). Currently, malic acid is mainly used as an acidulant and flavor enhancer in the food and beverage industries. Due to its more intense acid taste and better taste retention compared with citric acid, L-malic acid is becoming one of the most widely used organic acidulants. In the pharmaceutical industry, L-malic acid is used to improve the absorption of drugs and is used in amino acid infusions for the treatment of liver dysfunction or high blood ammonia . A mixture of calcium citrate and calcium malate is a commonly used source of calcium for improved bone strength without increasing the risk of kidney stones. Other commercial applications include metal cleaning, finishing, animal feed and chemical synthesis of biodegradable polymers, such as polymalic acid (PMA).

The primary commercial production of malic acid is currently based on petrochemical routes, such as the hydration of maleic anhydride generated from the oxidation of benzene or butane at high temperature and high pressure, yielding a racemic mixture of D- and L-malic acid. Malic acid has an asymmetric carbon and therefore it occurs in two isomers. Enantiopure L-malic acid is the physiological form present in all living organisms, ranging from bacteria to humans, while D-malic acid is rare in nature and difficult to assimilate by humans, thus it is not applicable to very young infants and elderly people. In 1970, the U.S. FDA ruled that DL-malic acid could not be used as an additive in infant food. Enzymatic conversion is an alternative process for synthesis of L-malic acid, using either immobilized fumarate hydratase or whole cells (Brevibacterium ammoniagenes or Saccharomyces cerevisiae) containing the enzyme fumarate hydratase to catalyze the conversion of fumarate into malic acid . However, the expensive purification of fumarate hydratase and difficult separation of L-malic acid from the unreacted substrate greatly increased the cost of L-malic acid production. In addition, substrates such as maleic anhydride or fumarate are derived from non-sustainable petroleum, and the upward trend in the cost of finite petroleum resources further hampered the expansion of the malic acid market. With the increasingly severe challenges related to the depletion of fossil-based resources as well as environmental issues, ecofriendly sustainable microbial fermentative production of malic acid has been given more attention. A lot of progresses has been made in the development of engineered strains or processes in recent years. Fermentation process of L-malic acid overcomes the dependence on petrochemical raw materials, is considered to be the most promising method.