The reaction sequence in ergothioneine biosynthesis: hercynine as an intermediate.

Ergothioneine can be synthesized by the mold, Neurospora crassa, from the amino acids, histidine, methionine, and cysteine (1). The intact histidine molecule is used in the synthesis, and the three methyl groups of the betaine moiety can be derived from methionine by a triple transmethylation process (2). Cysteine appears to be an immediate precursor of the sulfur atom of the thiolimidazole ring. In this paper we present data which establish the sequence of these biosynthetic reactions. provide data which show that hercynine is an intermediate compound in the biosynthesis of ergothioneine.