Ergothioneine is a multifunctional physiological cytoprotector, with broad application in foods, beverage, medicine, cosmetics and so on. Biosynthesis is an increasingly favored method in the production of ergothioneine. This paper summarizes the new progress in the identification of key pathways, the mining of key enzymes, and the development of natural edible mushroom species and high-yield engineering strains for ergothioneine biosynthesis in recent years. Through this review, we aim to reveal the molecular mechanism of ergothioneine biosynthesis and then employ the methods of fermentation engineering, metabolic engineering, and synthetic biology to greatly increase the yield of ergothioneine.
Antioxidants ; Ergothioneine/metabolism* ; Fermentation ; Metabolic Engineering

Ergothioneine (ERG) is a natural antioxidant that has been widely used in the fields of food, medicine and cosmetics. Compared with traditional plant extraction and chemical synthesis approaches, microbial synthesis of ergothioneine has many advantages, such as the short production cycle and low cost, and thus has attracted intensive attention. In order to engineer an ergothioneine high-yielding Escherichia coli strain, the ergothioneine synthesis gene cluster egtABCDE from Mycobacterium smegmatis and egt1 from Schizosaccharomyces pombe were introduced into E. coli BL21(DE3) to generate a strain E1-A1 harboring the ergothioneine biosynthesis pathway. As a result, (95.58±3.2) mg/L ergothioneine was produced in flask cultures. To further increase ergothioneine yield, the relevant enzymes for biosynthesis of histidine, methionine, and cysteine, the three precursor amino acids of ergothioneine, were overexpressed. Individual overexpression of serA^T410STOP and thrA resulted in an ergothioneine titer of (134.83±4.22) mg/L and (130.26±3.34) mg/L, respectively, while co-overexpression of serA^T410STOP and thrA increased the production of ergothioneine to (144.97±5.40) mg/L. Eventually, by adopting a fed-batch fermentation strategy in 3 L fermenter, the optimized strain E1-A1-thrA-serA^* produced 548.75 mg/L and 710.53 mg/L ergothioneine in glucose inorganic salt medium and rich medium, respectively.
Culture Media ; Ergothioneine/metabolism* ; Escherichia coli/metabolism* ; Fermentation ; Histidine/metabolism* ; Metabolic Engineering

Ergothioneine is widely distributed in biological systems, particularly in red blood cells of animals. However, it's functional role in human body is not well understood. In order to investigate the biochemical effect of L-ergothioneine, its concentration changes in human blood with respect to ages in healthy individuals was first investigated. L-ergothioneine concentrations in the blood of Saudi males from western province at different stages of life were measured by the procedure of Carlsson et al., 1974. At early stages of life (1-10 years), the concentrations of LER is 1.5-2.0 mg/100 ml. It increases gradually at the age of 11-18 years where it reaches the maximum value of 3.7 mg/100 ml. Then, it declines gradually to 3.0-2.3 mg/ 100 ml during the period of 19-50 years. An increase in the level of LER (2.8 mg/100 ml) was seen at the age of 51+.
Adolescence ; Adult ; Age Factors ; Child ; Child, Preschool ; Ergothioneine/*blood ; Erythrocytes/*chemistry/metabolism ; Human ; Male ; Middle Age ; Saudi Arabia ; Spectrophotometry/methods ; Support, Non-U.S. Gov't