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Review
. 2025 Apr 12;109(1):93.
doi: 10.1007/s00253-025-13476-4.

Biosynthesis of ergothioneine: current state, achievements, and perspectives

Shun Sato  1 , Azusa Saika  1 , Tatsuyuki Koshiyama  2 , Yukihiro Higashiyama  2 , Tokuma Fukuoka  1 , Tomotake Morita  3
Affiliations
Review

Biosynthesis of ergothioneine: current state, achievements, and perspectives

Shun Sato et al. Appl Microbiol Biotechnol. .

Abstract

Ergothioneine (EGT) is a derivative of the amino acid L-histidine that is well known for its strong antioxidant properties. Recent studies on the functional characterization of EGT in both in vivo and in vitro systems have demonstrated its potential applications in pharmaceuticals, food, and cosmetics. The growing demand for EGT in novel applications necessitates the development of safe and cost-effective mass production technologies. Consequently, microbial fermentation for EGT biosynthesis has attracted significant attention. This review focuses on the biosynthesis of EGT via microbial fermentation, explores its biosynthetic mechanisms, and summarizes the latest advancements for industrial EGT production using engineered microbial strains. KEY POINTS: • Ergothioneine (EGT) is an L-histidine derivative with strong antioxidant property. • Recent studies have revealed certain groups of microbes produce EGT naturally. • Superior EGT producers by genetic modification have been created.

Keywords: Antioxidant; Basidiomycetes; Biosynthesis; Ergothioneine.

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Conflict of interest statement

Declarations. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Conflict of interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Chemical structure of EGT. The tautomer forms of thiol (left) and thione (right) are shown
Scheme 1
Scheme 1
Cys, L-cysteine; 3-MPA, 3-mercaptopropionic acid; NBS, N-bromosuccinimide; PLP, pyridoxal phosphate
Fig. 2
Fig. 2
Biosynthetic pathways for EGT production in Mycobacterium smegmatis (left), Neurospora crassa (center), and Chlorobium limicola (right). Met, L-methionine; SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine; Cys, L-cysteine; γ-GluCys, γ-glutamylcysteine
See this image and copyright information in PMC

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