Greenberg J T, Demple B
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
EMBO J. 1988 Aug;7(8):2611-7. doi: 10.1002/j.1460-2075.1988.tb03111.x.
Mutations that suppressed the H2O2 sensitivity of Escherichia coli oxyR- strains caused elevated levels of one three enzymes that destroy organic and hydrogen peroxides: catalase-hydroperoxidase I (the katG gene product), catalase-hydroperoxidase II (controlled by katEF) or alkyl hydroperoxide reductase (specified by the ahp genes). The continuous high-level expression of any one of these enzymes also conferred resistance in an oxyR deletion mutant against other compounds such as N-ethylmaleimide and the superoxide-generator menadione. Overproduction of alkyl hydroperoxide reductase, but not of the catalases, gave resistance to the organic oxidant cumene hydroperoxide. The E. coli delta oxyR strains also exhibited a strongly elevated frequency of spontaneous mutagenesis, as reported for such mutants in Salmonella typhimurium. This mutagenesis was greatly diminished by the individual overexpression of these scavenging enzymes. All of these phenotypes--enzyme overproduction, resistance to oxidants and suppression of spontaneous mutagenesis--remained linked upon transduction of the mutant katG or ahp genes. Peroxides thus appear to mediate the toxicity of a variety of redox agents, and are produced in sufficient quantity during normal metabolism to cause a substantial increase in 'spontaneous' mutations in cells that lack adequate antioxidant defenses.
抑制大肠杆菌oxyR-菌株对过氧化氢敏感性的突变，导致三种能够破坏有机过氧化物和过氧化氢的酶水平升高：过氧化氢酶-氢过氧化物酶I（katG基因产物）、过氧化氢酶-氢过氧化物酶II（受katEF控制）或烷基氢过氧化物还原酶（由ahp基因指定）。这些酶中任何一种的持续高水平表达，也使oxyR缺失突变体对其他化合物如N-乙基马来酰亚胺和超氧化物生成剂甲萘醌产生抗性。烷基氢过氧化物还原酶的过量产生，而不是过氧化氢酶的过量产生，赋予了对有机氧化剂枯烯过氧化氢的抗性。如对鼠伤寒沙门氏菌此类突变体的报道一样，大肠杆菌ΔoxyR菌株也表现出自发突变频率大幅升高。这些清除酶的单独过表达极大地减少了这种诱变作用。在转导突变的katG或ahp基因后，所有这些表型——酶的过量产生、对氧化剂的抗性以及自发诱变的抑制——仍然相关联。因此，过氧化物似乎介导了多种氧化还原剂的毒性，并且在正常代谢过程中产生的量足以在缺乏足够抗氧化防御的细胞中导致“自发”突变大幅增加。
