Biosynthesis of ergothioneine: current state, achievements, and perspectives

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.

Fig. 1

Chemical structure of EGT. The tautomer forms of thiol (left) and thione (right) are shown

Scheme 1

Cys, L-cysteine; 3-MPA, 3-mercaptopropionic acid; NBS, N-bromosuccinimide; PLP, pyridoxal phosphate

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