L-Alanine - CAS 56-41-7

L-alanine is extensively used in chemical, food, and medicine industries. Industrial production of L-alanine has been mainly based on the enzymatic process using petroleum-based L-aspartic acid as the substrate. L-alanine production from renewable biomass using microbial fermentation process is an alternative route. Many microorganisms can naturally produce L-alanine using aminotransferase or L-alanine dehydrogenase. However, production of L-alanine using the native strains has been limited due to their low yields and productivities. In this review, metabolic engineering of microorganisms for L-alanine production was summarized. Among them, the Escherichia coli strains developed by Dr. Lonnie Ingram's group which can produce L-alanine with anaerobic fermentation process had several advantages, especially having high L-alanine yield, and it was the first one that realized commercialization. L-alanine is also the first amino acid that could be industrially produced by anaerobic fermentation.

Alanine aminotransferase (Alt, L-alanine:2-oxoglutalate aminotransferase) is a pyridoxal enzyme which catalyses the reversible interconversion of L-alanine and 2-oxoglutalate to pyruvate and L-glutamate. The enzyme is widely distributed in various tissues from animals and even in some kind of plants. Isoenzymes of human ALT localize in the cytosol (c-ALT) and mitochondria (m-ALT) of tissues such as liver, kidney, skeletal and cardiac muscles. Amino acid sequence of c-ALT from rat and human liver has been wholly determined by Ishiguro et al. It is suggested that c-ALT is associated to the utilization of pyruvate in glycolysis and m-ALT is involved in the conversion of alanine to pyruvate for gluconeogenesis.

L-alanine possesses extensive physiological functionality and tremendous pharmacological significance, therefore could be considered as potential ingredient for food, pharmaceutical, and personal care products. However, therapeutic properties of L-alanine still need to be addressed in detail to further strengthen its utilization as a viable ingredient for developing natural therapeutics with minimum side effects. Thus, the present study was aimed to explore the anticipated therapeutic potential of L-alanine, produced microbially using a lactic acid bacterial strain Pediococcus acidilactici BD16 (alaD + ) expressing L-alanine dehydrogenase enzyme. The anticipated therapeutic potential of L-alanine was assessed in terms of anti-proliferative, anti-bacterial, and anti-urolithiatic properties. Anti-bacterial assays revealed that L-alanine successfully inhibited growth and in vitro proliferation of important human pathogens including Enterococcus faecalis, Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, Streptococcus mutans, and Vibrio cholerae in a concentration-dependent manner. Current investigation has also revealed its significant anti-proliferative potential against human lung adenocarcinoma (A549; IC 50 7.32 μM) and mammary gland adenocarcinoma (MCF-7; IC 50 8.81 μM) cells. The anti-urolithiatic potential of L-alanine was augmented over three different phases, viz., nucleation inhibition, aggregation inhibition, and oxalate depletion. Further, an in vitro cell culture-based kidney stone dissolution model using HEK293-T cells was also established to further strengthen its anti-urolithiatic potential. This is probably the first in vitro cell culture-based model which experimentally validates the immense therapeutic efficacy of L-alanine in treating urolithiasis disease. KEY POINTS: • Assessment of therapeutic potential of L-alanine produced by LAB. • L-alanine exhibited significant anti-proliferative and anti-bacterial activities. • L-alanine as potential anti-urolithiatic agent.