科學家改造了大腸桿菌從而讓它大量制造出了一種酶,，這種酶可以保護小鼠免遭一種有機磷酸酯殺蟲劑的毒性作用。
這種稱為diazoxon的殺蟲劑是一種有機磷酸酯,，它是包括VX和沙林等神經(jīng)毒氣在內的一族化合物中的一員,。Richard Stevens及其同事說他們的體系有可能讓科學家去開發(fā)改進型的酶,，用于治療目的和防御神經(jīng)毒劑。這種哺乳動物酶對氧磷酶1（PON1）是一種催化劑,，因此很小劑量的PON1就可以用于防范血流中的大量毒劑,。在此前的研究中，這組作者證明了缺乏PON1 基因的轉基因小鼠可以通過注射人類PON1從而不受兩種有機磷酸酯的傷害,。
在這項新的研究中,，這組作者在大腸桿菌中表達了兩種類型的PON1：人類版本的酶和包含了兔子身上發(fā)現(xiàn)的一個關鍵的氨基酸替代的人類版本的酶。第二種酶在試管試驗中能更有效地對抗幾種有機磷酸酯,，而且還能保護PON1基因敲除小鼠不受幾倍于致死劑量的diazoxon的傷害,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS Published online before print August 18, 2008, doi: 10.1073/pnas.0805865105
Engineered recombinant human paraoxonase 1 (rHuPON1) purified from Escherichia coli protects against organophosphate poisoning
Richard C. Stevens, Stephanie M. Suzuki, Toby B. Cole, Sarah S. Park, Rebecca J. Richter, and Clement E. Furlong*
Abstract
The high-density lipoprotein-associated enzyme paraoxonase 1 (PON1) hydrolyzes lactones, aromatic esters, and neurotoxic organophosphorus (OP) compounds, including insecticide metabolites and nerve agents. Experiments with mice lacking PON1 (PON1−/− mice) have established that plasma PON1 protects against chlorpyrifos/chlorpyrifos-oxon and diazinon/diazoxon (DZO) exposure but does not protect against parathion/paraoxon or nerve agents. The catalytic efficiency of PON1 determines whether or not it will protect against a given OP exposure. Expression of active recombinant human PON1 (rHuPON1) in Escherichia coli provides a system in which PON1 can be engineered to achieve a catalytic efficiency sufficient to protect against or treat specific OP exposures. Here, we describe the generation of highly purified engineered rHuPON1K192 that protects against DZO exposure when injected into PON1−/− mice. The injected rHuPON1 is nontoxic, persists in serum for at least 2 days after injection, and provides protection against DZO exposures of at least three times the median lethal dose value.
