The biology of ergothioneine, an antioxidant nutraceutical

Abstract

Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.

Keywords: Cytoprotectants; Ergothioneine; Nutraceuticals; Oxidative stress; SLC22A4.

Fig. 1.

Structures of ergothioneine and related molecules. For a colour figure, see the online version of the paper.

Fig. 2.

The two main pathways of aerobic ergothioneine (ERG) biosynthesis, noting the relevant enzymes and thumbnails of three-dimensional structures where known. SAM, S-adenosyl methionine. For a colour figure, see the online version of the paper.

Fig. 3.

Alignment of Neurospora crassa Egt1 and N-terminal part of Mycobacterium tuberculosis EgtD. For a colour figure, see the online version of the paper.

Fig. 4.

Differences in expression of SLC22A4 transcript in a series of mammalian cell lines. Data are from Thul et al.⁽¹⁸⁶⁾ and O’Hagan et al.⁽¹¹⁹⁾. For a colour figure, see the online version of the paper.

Fig. 5.

Superoxide and peroxide are produced by 1- and 2-electron reduction of dioxygen by the mammalian respiratory chain. For a colour figure, see the online version of the paper.

Fig. 6.

Catalytic roles of unliganded iron in hydroxyl radical production via the Fenton and Haber–Weiss reactions. This can be stopped by ensuring that iron is fully liganded. For a colour figure, see the online version of the paper.

Fig. 7.

Overview of some of the effects of ergothioneine in mammalian systems. For a colour figure, see the online version of the paper.