科学家改造了大肠杆菌从而让它大量制造出了一种酶，这种酶可以保护小鼠免遭一种有机磷酸酯杀虫剂的毒性作用。
这种称为diazoxon的杀虫剂是一种有机磷酸酯，它是包括VX和沙林等神经毒气在内的一族化合物中的一员。Richard Stevens及其同事说他们的体系有可能让科学家去开发改进型的酶，用于治疗目的和防御神经毒剂。这种哺乳动物酶对氧磷酶1（PON1）是一种催化剂，因此很小剂量的PON1就可以用于防范血流中的大量毒剂。在此前的研究中，这组作者证明了缺乏PON1 基因的转基因小鼠可以通过注射人类PON1从而不受两种有机磷酸酯的伤害。
在这项新的研究中，这组作者在大肠杆菌中表达了两种类型的PON1：人类版本的酶和包含了兔子身上发现的一个关键的氨基酸替代的人类版本的酶。第二种酶在试管试验中能更有效地对抗几种有机磷酸酯，而且还能保护PON1基因敲除小鼠不受几倍于致死剂量的diazoxon的伤害。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
