title: Bioinformatic and biochemical characterizations of C-S bond formation and cleavage enzymes in the fungus Neurospora crassa ergothioneine biosynthetic pathway.
abstract: Ergothioneine is a histidine thiol derivative. Its mycobacterial biosynthetic pathway has five steps (EgtA-E catalysis) with two novel reactions: a mononuclear nonheme iron enzyme (EgtB) catalyzed oxidative C-S bond formation and a PLP-mediated C-S lyase (EgtE) reaction. Our bioinformatic and biochemical analyses indicate that the fungus Neurospora crassa has a more concise ergothioneine biosynthetic pathway because its nonheme iron enzyme, Egt1, makes use of cysteine instead of γ-Glu-Cys as the substrate. Such a change of substrate preference eliminates the competition between ergothioneine and glutathione biosyntheses. In addition, we have identified the N. crassa C-S lyase (NCU11365) and reconstituted its activity in vitro, which makes the future ergothioneine production through metabolic engineering feasible.
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou, P. R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Hu
authors.forename: Heng
authors.initials: H
authors.lastname: Song
authors.forename: Ampon
authors.initials: A
authors.lastname: Sae Her
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Bak
authors.forename: Nathchar
authors.initials: N
authors.lastname: Naowarojna
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Elliott
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Pinghua
authors.initials: P
authors.lastname: Liu
mesh_terms: D053898:Biosynthetic Pathways; D002384:Catalysis; D004151:Dipeptides / Q000378:metabolism; D004880:Ergothioneine / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism*; D006639:Histidine / Q000031:analogs & derivatives / Q000378:metabolism; D015394:Molecular Structure; D009492:Neurospora crassa / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D004151:Dipeptides; D006639:Histidine; D004880:Ergothioneine; C017341:gamma-glutamylcysteine