title: Mechanistic Investigation on ROS Resistance of Phosphorothioated DNA.
abstract: Phosphorothioated DNA (PT-DNA) exhibits a mild anti-oxidant property both in vivo and in vitro. It was found that 8-OHdG and ROS levels were significantly lower in dnd+ (i.e. S+) E. coli., compared to a dnd- (i.e. S-) strain. Furthermore, different from traditional antioxidants, phosphorothioate compound presents an unexpectedly high capacity to quench hydroxyl radical. Oxidative product analysis by liquid chromatography-mass spectrometry and quantum mechanistic computation supported its unique anti-oxidant characteristic of the hydroxyl selectivity: phosphorothioate donates an electron to either hydroxyl radical or guanine radical derived from hydroxyl radical, leading to a PS•radical; a complex of PS•radical and OH-(i.e. the reductive product of hydroxyl radical) releases a highly reductive HS•radical, which scavenges more equivalents of oxidants in the way to high-covalent sulphur compounds such as sulphur, sulphite and sulphate. The PS-PO conversion (PS and PO denote phosphorus-sulphur and phosphorus-oxygen compounds, respectively) made a switch of extremely oxidative OH•to highly reductive HS•species, endowing PT-DNA with the observed high capacity in hydroxyl-radical neutralization. This plausible mechanism provides partial rationale as to why bacteria develop the resource-demanding PT modification on guanine-neighboring phosphates in genome.
authors.affiliation: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic &Developmental Sciences, MOE-LSB and MOE-LSC, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic &Developmental Sciences, MOE-LSB and MOE-LSC, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic &Developmental Sciences, MOE-LSB and MOE-LSC, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic &Developmental Sciences, MOE-LSB and MOE-LSC, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic &Developmental Sciences, MOE-LSB and MOE-LSC, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Linquan
authors.initials: L
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic &Developmental Sciences, MOE-LSB and MOE-LSC, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Jingdan
authors.initials: J
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic &Developmental Sciences, MOE-LSB and MOE-LSC, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic &Developmental Sciences, MOE-LSB and MOE-LSC, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic &Developmental Sciences, MOE-LSB and MOE-LSC, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Yi-Lei
authors.initials: YL
authors.lastname: Zhao
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D004269:DNA, Bacterial / Q000737:chemistry* / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics; D008401:Gas Chromatography-Mass Spectrometry; D017665:Hydroxyl Radical / Q000494:pharmacology; D018384:Oxidative Stress; D010710:Phosphates / Q000378:metabolism*; D011789:Quantum Theory; D017382:Reactive Oxygen Species / Q000032:analysis*
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D010710:Phosphates; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; C083120:phosphorodithioic acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine