γ-Glutamyl compounds and their enzymatic production using bacterial γ-glutamyltranspeptidase

Abstract

Some amino acids and peptides, which have low solubility in water, become much more soluble following gamma-glutamylation. Compounds become more stable in the blood stream with gamma-glutamylation. Several gamma-glutamyl compounds are known to have favorable physiological effects on mammals. Gamma-glutamylation can improve taste and can stabilize glutamine in aqueous solution. Because of such favorable features, gamma-glutamyl compounds are very attractive. However, only a small number of gamma-glutamyl amino acids have been studied although many other gamma-glutamyl compounds may have characteristics that will benefit humans. This is mainly because gamma-glutamyl compounds have not been readily available. An efficient and simple method of producing various gamma-glutamyl compounds, especially gamma-glutamyl amino acids, using bacterial gamma-glutamyltranspeptidase has been developed. With this method, modifications of reactive groups of the substrate and energy source such as ATP are not required, and a wide-range of gamma-glutamyl compounds can be synthesized. Moreover, bacterial gamma-glutamyltranspeptidase, a catalyst for this method, is readily available from the strain over-producing this enzyme. The superiority of producing gamma-glutamyl compounds with bacterial gamma-glutamyltranspeptidase over other methods of production is discussed.

Synthesis of theanine from glutamic acid γ-methyl ester and ethylamine catalyzed by Escherichia coli having γ-glutamyltranspeptidase activity

“…A series of c-glutamyl compounds, including c-Lglutamylcysteine, c-L-glutamyl-L-DOPA, theanine (c-glutamylethylamide) and c-D-glutamyl-L-tryptophan, can be produced in this way (Bridge and Zarka 2006;Suzuki et al 2007). The usual substrate for theanine synthesis catalyzed by GGT is glutamine, but our research shows that glutamic acid c-methyl ester (GAME) also to be an effective c-glutamyl donor.…”

Untargeted metabolic footprinting reveals a surprising breadth of metabolite uptake and release by Synechococcus sp. PCC 7002

“…28 We previously identified a series of g-glutamyl dipeptides of these amino acids in Synechococcus 14 suggesting a mechanism to retain these amino acids inside cells as g-glutamylation increases solubility of these amino acids preventing leakage through cell membranes. 29 Synechococcus was found to consume metabolites having the most intense peaks in metabolite profiles of its own extract. A total of 29 metabolites from SE were found to be significantly consumed (p-value o 0.05; Table S1) including metabolites we previously classified as ''unexpected'' as they were not present in the draft metabolic network of Synechococcus reconstructed based on genome annotation.…”

Thermo- and salt-tolerant chitosan cross-linked γ-glutamyl transpeptidase from Bacillus licheniformis ER15

“…However, in the absence of any specific acceptor, enzyme transfers the ␥-glutamyl moiety to water molecule, hence, showing hydrolytic activity. Microbial GGTs have found major application in the synthesis of ␥-glutamyl compounds that have usage in pharmaceutical, food and medical sectors [2]. In food industries, GGTs have been utilized for the production of theanine [3], for debittering of bitter amino acids [4] and to increase the 'umami' taste of soy sauce [5].…”