Science：抗癌生物碱Noscapine生物合成途径研究新进展

5月31日，Science杂志在线报道了抗癌生物碱诺斯卡品（Noscapine）生物合成途径的最新研究进展。新发现的合成途径关键酶复合基因簇加深了我们对该途径的认识，为人类合成利用Noscapine抗击肿瘤创造了新的契机。

Noscapine是从鸦片罂粟中提取的一种抗肿瘤生物碱。它可在人类细胞中结合微管蛋白，将细胞周期阻断在有丝分裂中期。阐明其生物合成途径将促进Noscapine及其相关生物活性分子的商业化生产。

转录组分析显示，在一种Noscapine高含量的鸦片罂粟品种HN1中，编码5个独特酶家族的10个基因呈排他性表达。对次级作图群体的分析显示，这10个基因在HN1种罂粟中紧密联系在一起。

细菌人工染色体序列分析证实，它们作为产生植物生物碱的一个复合基因簇而存在。利用病毒诱导把这些基因沉默，将导致此生物合成途径的中间产物堆积。这说明，这10个基因的功能是与Noscapine生物合成息息相关的。

据此，研究者提出了Noscapine生物合成途径的新的理论。

doi:10.1016/j.cell.2011.10.017

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 A Papaver somniferum 10-Gene Cluster for Synthesis of the Anticancer Alkaloid Noscapine

Thilo Winzer1, Valeria Gazda1, Zhesi He1, Filip Kaminski1, Marcelo Kern1, Tony R. Larson1, Yi Li1, Fergus Meade1, Roxana Teodor1, Fabián E. Vaistij1, Carol Walker2, Tim A. Bowser2, Ian A. Graham1,*

Noscapine is an antitumor alkaloid from opium poppy that binds tubulin, arrests metaphase, and induces apoptosis in dividing human cells. Elucidation of the biosynthetic pathway will enable improvement in commercial production of noscapine and related bioactive molecules. Transcriptomic analysis revealed the exclusive expression of 10 genes encoding five distinct enzyme classes in a high noscapine-producing poppy variety, HN1. Analysis of an F2 mapping population indicated the genes are tightly linked in HN1, and bacterial artificial chromosome sequencing confirmed they exist as a complex gene cluster for plant alkaloids. Virus-induced gene silencing resulted in accumulation of pathway intermediates allowing gene function to be linked to noscapine synthesis and a novel biosynthetic pathway to be proposed.