5月31日,，Science雜志在線報(bào)道了抗癌生物堿諾斯卡品（Noscapine）生物合成途徑的最新研究進(jìn)展。新發(fā)現(xiàn)的合成途徑關(guān)鍵酶復(fù)合基因簇加深了我們對該途徑的認(rèn)識,，為人類合成利用Noscapine抗擊腫瘤創(chuàng)造了新的契機(jī),。
Noscapine是從鴉片罌粟中提取的一種抗腫瘤生物堿。它可在人類細(xì)胞中結(jié)合微管蛋白,，將細(xì)胞周期阻斷在有絲分裂中期,。闡明其生物合成途徑將促進(jìn)Noscapine及其相關(guān)生物活性分子的商業(yè)化生產(chǎn)。
轉(zhuǎn)錄組分析顯示,，在一種Noscapine高含量的鴉片罌粟品種HN1中,，編碼5個(gè)獨(dú)特酶家族的10個(gè)基因呈排他性表達(dá)。對次級作圖群體的分析顯示,，這10個(gè)基因在HN1種罌粟中緊密聯(lián)系在一起,。
細(xì)菌人工染色體序列分析證實(shí)，它們作為產(chǎn)生植物生物堿的一個(gè)復(fù)合基因簇而存在,。利用病毒誘導(dǎo)把這些基因沉默,，將導(dǎo)致此生物合成途徑的中間產(chǎn)物堆積。這說明,，這10個(gè)基因的功能是與Noscapine生物合成息息相關(guān)的,。
據(jù)此，研究者提出了Noscapine生物合成途徑的新的理論,。（生物谷bioon.com)
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.
