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Biotransformation of N-Nitrosodimethylamine by Pseudomonas mendocina KR1

机译:Mendocina KR1对N-亚硝基二甲胺的生物转化

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N-Nitrosodimethylamine (NDMA) is a potent carcinogen and an emerging contaminant in groundwater and drinking water. The metabolism of NDMA in mammalian cells has been widely studied, but little information is available concerning the microbial transformation of this compound. The objective of this study was to elucidate the pathway(s) of NDMA biotransformation by Pseudomonas mendocina KR1, a strain that possesses toluene-4-monooxygenase (T4MO). P. mendocina KR1 was observed to initially oxidize NDMA to N-nitrodimethylamine (NTDMA), a novel metabolite. The use of 18O2 and H218O revealed that the oxygen added to NDMA to produce NTDMA was derived from atmospheric O2. Experiments performed with a pseudomonad expressing cloned T4MO confirmed that T4MO catalyzes this initial reaction. The NTDMA produced by P. mendocina KR1 did not accumulate, but rather it was metabolized further to produce N-nitromethylamine (88 to 94% recovery) and a trace amount of formaldehyde (HCHO). Small quantities of methanol (CH3OH) were also detected when the strain was incubated with NDMA but not during incubation with either NTDMA or HCHO. The formation of methanol is hypothesized to occur via a second, minor pathway mediated by an initial α-hydroxylation of the nitrosamine. Strain KR1 did not grow on NDMA or mineralize significant quantities of the compound to carbon dioxide, suggesting that the degradation process is cometabolic.
机译:N-亚硝基二甲胺(NDMA)是强力致癌物,是地下水和饮用水中的新兴污染物。已经广泛研究了哺乳动物细胞中NDMA的代谢,但是关于该化合物的微生物转化的信息很少。这项研究的目的是阐明门多氏假单胞菌KR1的NDMA生物转化途径,该菌株具有甲苯-4-单加氧酶(T4MO)。观察到P. mendocina KR1最初将NDMA氧化为一种新型代谢产物N-硝基二甲基胺(NTDMA)。 18O2和H218O的使用表明,添加到NDMA中以生成NTDMA的氧气来自大气中的O2。用表达克隆的T4MO的假单胞菌进行的实验证实,T4MO催化该初始反应。 Mendocina KR1产生的NTDMA并未积累,而是被进一步代谢产生N-硝基甲胺(回收率88%至94%)和微量甲醛(HCHO)。当菌株与NDMA一起温育而不是与NTDMA或HCHO温育时,也检测到少量甲醇(CH3OH)。据推测,甲醇的形成是通过亚硝胺的初始α-羟基化介导的第二小途径发生的。 KR1菌株未在NDMA上生长,也未将大量化合物矿化为二氧化碳,表明该降解过程是可代谢的。

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