Ergothioneine

Ergothioneine has been found in bacteria, plants, and animals, sometimes at high (millimolar) levels relative to the environment. Foods found to contain ergothioneine include liver, kidney, black beans, kidney bean, and oat bran, with the highest levels in bolete and oyster mushrooms, especially in Pleurotus citrinopileatus. Levels can be variable, even within species and some tissues can contain much more than others. In the human body, the largest amounts of ergothioneine are found in erythrocytes, eye lens, semen, and skin. Although many species contain ergothioneine, only a few make it; the others absorb it from their diet or, in the case of plants, from their environment. Biosynthesis has been detected in Actinomycetota, such as Mycobacterium smegmatis and certain fungi, such as Neurospora crassa (red bread mold) Biosynthetic pathway The metabolic pathway to produce ergothioneine starts with the methylation of histidine to produce histidine betaine (hercynine). The sulfur atom is then incorporated from cysteine. The biosynthetic genes of ergothioneine have been described in detail for Mycobacterium smegmatis, Neurospora crassa, Schizosaccharomyces pombe (with homologues in Aspergillus, a genus important in food fermentation), and Caldithrix abyssi. Different groups of organisms use different approaches to sulfur-addition. Aerobic bacteria and fungi use an O2-dependent reaction that is catalyzed by a mononuclear non-heme iron enzyme, with cysteine or γ-glutamylcysteine as the sulfur source. Green sulfur bacteria and some archaea use a rhodanese-like sulfur transferase to perform oxidative polar substitution. Caldithrix uses a metallopterin-dependent bifunctional enzyme that combines an N-terminal domain similar to a tungsten-dependent acetylene hydratase and a C-terminal cysteine desulfurase domain. Homologs of the Caldithrix system are found in anaerobic bacteria and some archaea. In 2025, an even higher concentration of 7200 mg/L was achieved with E. coli without requiring the feeding of expensive methionine (methyl source) or cysteine by adding genes to have the bacteria make its own. == Structure ==

Ergothioneine is a thiourea derivative of the betaine of histidine and contains a sulfur atom bonded to the 2-position of the imidazole ring. Typical of thioureas, ergothioneine is less reactive than typical thiols such as glutathione towards alkylating agents like maleimides. It also resists oxidation by air. ==Ergothioneine derivatives==

Various derivatives of ergothioneine have been reported in the literature, such as S-methyl-ergothioneine or selenium-containing selenoneine. The latter is made using the same biosynthetic pathway as ergothioneine when selenocysteine is present. ==Preliminary research==

Although ergothioneine is under preliminary research, its physiological role in vivo has not been determined. Mammals use the OCTN1 transporter to move ergothioneine into cells. Knockout of this gene in mouse and zebrafish models produces no substantial overt defect, though stress does amplify the differences. ==Safe intake levels==

The Panel on Dietetic Products for the European Food Safety Authority reported safe daily limits of 2.82 mg/kg of body weight for infants, 3.39 mg/kg for small children, and 1.31 mg/kg for adults, including pregnant and breastfeeding women. == See also ==