Publications

• Ergothioneine biosynthetic methyltransferase EgtD reveals the structural basis of aromatic amino acid betaine biosynthesis.

  Vit A., Misson L., Blankenfeldt W., Seebeck F.P.

  Ergothioneine is an N-α-trimethyl-2-thiohistidine derivative that occurs in human, plant, fungal, and bacterial cells. Biosynthesis of this redox-active betaine starts with trimethylation of the α-amino group of histidine. The three consecutive methyl transfers are catalyzed by the S-adenosylmethi ... >> More

  Ergothioneine is an N-α-trimethyl-2-thiohistidine derivative that occurs in human, plant, fungal, and bacterial cells. Biosynthesis of this redox-active betaine starts with trimethylation of the α-amino group of histidine. The three consecutive methyl transfers are catalyzed by the S-adenosylmethionine-dependent methyltransferase EgtD. Three crystal structures of this enzyme in the absence and in the presence of N-α-dimethylhistidine and S-adenosylhomocysteine implicate a preorganized array of hydrophilic interactions as the determinants for substrate specificity and apparent processivity. We identified two active site mutations that change the substrate specificity of EgtD 10(7)-fold and transform the histidine-methyltransferase into a proficient tryptophan-methyltransferase. Finally, a genomic search for EgtD homologues in fungal genomes revealed tyrosine and tryptophan trimethylation activity as a frequent trait in ascomycetous and basidomycetous fungi. << Less

  ChemBioChem 16:119-125(2015) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• The enzymatic alpha-N-methylation of histidine.

  Ishikawa Y., Melville D.B.

  J. Biol. Chem. 245:5967-5973(1970) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• In vitro reconstitution of Mycobacterial ergothioneine biosynthesis.

  Seebeck F.P.

  Ergothioneine is a histidine-derived thiol of bacterial and fungal origin that has also been isolated from animal and human tissue. Recent findings point to critical functions of ergothioneine in human physiology, but its role in microbial life is poorly understood. This report describes the ident ... >> More

  Ergothioneine is a histidine-derived thiol of bacterial and fungal origin that has also been isolated from animal and human tissue. Recent findings point to critical functions of ergothioneine in human physiology, but its role in microbial life is poorly understood. This report describes the identification of the ergothioneine biosynthetic gene cluster from mycobacteria and in vitro reconstitution of this process using recombinant proteins from Mycobacterium smegmatis. The key reactions are catalyzed by a methyltransferase that transfers three methyl groups to the alpha-amino moiety of histidine and an iron(II)-dependent enzyme that catalyzes oxidative sulfurization of trimethylhistidine. A search for homologous genes indicated that ergothioneine production is a frequent trait among fungi, actinobacteria, and cyanobacteria but also occurs in numerous bacteroidetes and proteobacteria. << Less

  J. Am. Chem. Soc. 132:6632-6633(2010) [PubMed] [EuropePMC]

  This publication is cited by 8 other entries.