title: Oxidative-stress detoxification and signalling in cyanobacteria: the crucial glutathione synthesis pathway supports the production of ergothioneine and ophthalmate.
abstract: Using genetics and metabolomics we investigated the synthesis (gshA and gshB genes) and catabolism (ggt) of the conserved antioxidant glutathione in the model cyanobacterium Synechocystis PCC6803. These three genes are crucial to Synechocystis, in agreement with the proposed invention of glutathione by ancient cyanobacteria to protect themselves against the toxicity of oxygen they produced through photosynthesis. Consistent with their indispensability, gshA and gshB also operate in the production of another antioxidant, ergothioneine, as well as of the glutathione analogues ophthalmate and norophthalmate. Furthermore, we show that glutathione, ophthalmate and norophthalmate are accumulated in cells stressed by glucose, and that the two glutathione-dependent glyoxalase enzymes operate in the protection against glucose and its catabolite methylglyoxal. These findings are interesting because ophthalmate and norophthalmate were observed only in mammals so far, where ophthalmate is regarded as a biomarker of glutathione depletion. Instead, our data suggest that ophthalmate and norophthalmate are stress-induced markers of cysteine depletion triggered by its accelerated incorporation into glutathione, to face its increased demand for detoxification purposes. Hence, Synechocystis is an attractive model for the analysis of the role of glutathione, ergothioneine, ophthalmate and norophthalmate, in signalling and detoxification of oxidants and metabolic by-products.
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Kinsley
authors.initials: K
authors.lastname: Narainsamy
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Farci
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Braun
authors.affiliation: CEA, iBiTec-S, SPI, LEMM, Bat 136 CEA-Saclay, F-91191, Gif sur Yvette cedex, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Junot
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Cassier-Chauvat
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Chauvat
mesh_terms: D053898:Biosynthetic Pathways; D000458:Cyanobacteria / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004880:Ergothioneine / Q000096:biosynthesis; D005798:Genes, Bacterial; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis; D008658:Inactivation, Metabolic; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D009842:Oligopeptides / Q000096:biosynthesis; D018384:Oxidative Stress; D011765:Pyruvaldehyde / Q000378:metabolism; D015398:Signal Transduction; D046939:Synechocystis / Q000378:metabolism
chemical_list: D009842:Oligopeptides; C016632:ophthalmic acid; D011765:Pyruvaldehyde; D004880:Ergothioneine; D007791:Lactoylglutathione Lyase; D005978:Glutathione; D005947:Glucose