Sunday, 4 July 2021

Gamma Polyglutamic Acid Finds Application as Immune-Stimulating and Anti-Tumor Agent at High Molecular Weight

 

Gamma polyglutamic acid


Gamma polyglutamic acid (PGA) is a polymer of the amino acid glutamic acid majorly produced by Bacillus subtilis, (a bacteria), B. amyloliquefaciens, B. megaterium, and B. licheniformis. It biodegradable, non-toxic and non-immunogenic. In gamma-PGA, the peptide bonds are between the amino group of GA and the carboxyl group at the end of the glutamic acid side chain. It stimulates and improves immune activity. Poly-γ-glutamic acid occurs naturally as a biopolymer. It is produced from repeating units of l-glutamic acid, d-glutamic acid or both. The properties of gamma--PGA vary significantly.
Gamma polyglutamic acid is a viscous substance produced during the fermentation of natto, a traditional Japanese food made from soy through fermentation by Bacillus subtilis and is rich in soybean protein, isoflavone, dietary fiber, and vitamin K, which are derived from soy and produced by Bacillus subtilis. High-gamma-polyglutamic acid meal suppresses insulin secretion more than the low gamma-polyglutamic acid meal. It finds application in the food, medical, cosmetic, animal feed, and wastewater industries. Ultra-high-molecular-weight gamma-PGA is water soluble, anionic, biodegradable, and edible. It finds application in cosmetics and skin care, bone care, hydrogel production, and nanoparticle for drug delivery system. At a high molecular weight, gamma-PGA can also be used as an immune-stimulating and anti-tumor agent.
This water-soluble polymer is made from D- and L-glutamic acid units, which are linked by amide bonds formed between alpha-amino and gamma-carboxylic acid groups. Gamma polyglutamic acid is used for protein crystallization, as a soft tissue adhesive and a non-viral vector for safe gene delivery. It is also used in many medical applications such as drug delivery. It is used in the food, cosmetic, and other industries due to its good biocompatibility. Optimized culture conditions help in high production of gamma-PGA productivity.
Glycerol can also be used in the production of gamma polyglutamic acid. Glycerol can help control the molecular weight of gamma PGA. Moreover, glycerol along with Tween-80 and dimethyl sulfoxide (DMSO) can be used to regulate the central carbon metabolic pathway and improve gamma-PGA biosynthesis by Bacillus subtilis CGMCC 0833. Several studies have also found that temperature control strategy can help improve gamma polyglutamic acid production and a stable metabolic mechanism of γ-PGA biosynthesis in Bacillus species. On the other hand, citric acid and oxalic acid have potential to support the overproduction of γ-PGA. In this process, oxalic acid causes enhanced level of pyruvate dehydrogenase (PDH) activity, which is important for glutamic acid synthesized de novo from glucose.

An efficient synthetic expression control sequence plays a major role in production of gamma polyglutamic acid using bacillus subtilis DB430, which possesses the gamma-PGA synthesis ywsC-ywtAB genes in its chromosome. No supplementation of extra glutamic acid or ammonium chloride is required in production of high levels of gamma-PGA using mutant B. subtilis PGA6-2. Wild and domestic strains of Bacillus subtilis can significantly affect the production of gamma-PGA. Several studies have found that domestic strain of B. subtilis fail to produce gamma-PGA.

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