Science争议性研究：制造吗啡的关键工具

2015-06-29 佚名生物通

发表在最新一期《科学》（Science）杂志上的一项研究揭示出了人们长期探索的一个基因，它似乎是合成吗啡类生物碱，包括止痛药吗啡和可待因的一个关键的关卡步骤。这一重要的研究发现可以让药物化学家们更容易地调整基因来生成副作用及成瘾性较小的新药物。但同时人们也担心这项研究工作将使得毒贩子像酿酒师酿造自己的啤酒一样，很快就能够轻易地制造出海洛因。这一称作为STORR的基因只存在于产生吗啡喃类的罂粟物种中

发表在最新一期《科学》（Science）杂志上的一项研究揭示出了人们长期探索的一个基因，它似乎是合成吗啡类生物碱，包括止痛药吗啡和可待因的一个关键的关卡步骤。

这一重要的研究发现可以让药物化学家们更容易地调整基因来生成副作用及成瘾性较小的新药物。但同时人们也担心这项研究工作将使得毒贩子像酿酒师酿造自己的啤酒一样，很快就能够轻易地制造出海洛因。

这一称作为STORR的基因只存在于产生吗啡喃类的罂粟物种中。在数百万年前，两个编码氧化酶和还原酶的基因发生融合便进化出了STORR基因。这一基因融合对吗啡的产生起着至关重要的作用。

科学家们希望这将使得人们能够培育出定制的罂粟品种，包括可以生成抗癌化合物那可丁（noscapine）的罂粟。发现STORR基因填补了在酵母一类的微生物中遗传操控吗啡生成所需的一套基因中一个缺失的部分（延伸阅读：科学家设计酵母菌用于吗啡合成）。这是否会在商业竞争中胜过植物源性的吗啡生产还需拭目以待。

研究人员是在鉴别无法生成吗啡或可待因，而是累积另一种化合物(S)-牛心果碱（reticuline）的罂粟植物时获得这一突破性发现的。这些植物被发现携带了STORR基因突变。这些突变给罂粟植物中生成吗啡的一条信号通路设置了障碍。科学家们证实，在酵母细胞中表达未突变的野生型基因可以克服这一障碍。

该研究的领导者、纽约大学生物学系新型农业产品中心的Ian Graham教授说：“植物生成了许多令人惊讶的天然化合物质。发现这一STORR融合基因让我们重新认识了罂粟植物是如何进化来生成已知对人类最有效的止痛药的。”

天然的吗啡类生物碱阿片制剂包括吗啡、可待因和蒂巴因。吗啡和可待因可直接用作为止痛药。蒂巴因则被广泛用作为合成许多半合成阿片制剂，包括氢可酮、氢吗啡酮、羟考酮和羟吗啡酮的原料。蒂巴因还可以用来合成阿片类拮抗剂纳洛酮——纳洛酮可以对抗阿片剂过量的副作用。

论文的主要作者Thilo Winzer博士说：“鸦片罂粟是最重要的药用植物之一。形成这一融合蛋白有可能是它能够合成出药物学上重要的吗啡烷生物碱的一个关键进化事件。”

发现STORR基因填补了在生物学系统中生产吗啡烷类所需的一套基因中一个缺失的部分。植物仍然是一个得到证实的有效生产系统，以相对较低的成本提供每公顷Kg量的活性药物成分(API)。发现STORR基因有可能促成了一条有待评估的替代供应线。

原始出处：

Winzer T1, Kern M1, King AJ1, Larson TR1, Teodor R1, Donninger S1, Li Y1, Dowle AA2, Cartwright J2, Bates R2, Ashford D2, Thomas J2, Walker C3, Bowser TA3, Graham IA1.Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein.Science. 2015 Jun 25. pii: aab1852. [Epub ahead of print]

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2015-07-04 huaxipanxing

看看

132 0
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2015-07-01 showtest

#吗啡#

37 0
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2015-07-01 jichang

#SCIE#

30 0
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2015-06-30 stupidox

嗯

118 0
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2015-06-30 1dd7b2bem83(暂无匿称)

m

116 0
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2015-06-29 owlhealth

细致

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