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Over 100 Million Years of Enzyme Evolution Underpinning the Production of Morphine in the Papaveraceae Family of Flowering Plants.
Plant Communications ( IF 10.5 ) Pub Date : 2020-02-05 , DOI: 10.1016/j.xplc.2020.100029
Yi Li 1 , Thilo Winzer 1 , Zhesi He 1 , Ian A Graham 1
Affiliation  

Phylogenomic analysis of whole genome sequences of five benzylisoquinoline alkaloid (BIA)-producing species from the Ranunculales and Proteales orders of flowering plants revealed the sequence and timing of evolutionary events leading to the diversification of these compounds. (S)-Reticuline is a pivotal intermediate in the synthesis of many BIAs and our analyses revealed parallel evolution between the two orders, which diverged ∼122 million years ago (MYA). Berberine is present in species across the entire Ranunculales, and we found co-evolution of genes essential for production of the protoberberine class. The benzophenanthridine class, which includes the antimicrobial compound sanguinarine, is specific to the Papaveraceae family of Ranunculales, and biosynthetic genes emerged after the split with the Ranunculaceae family ∼110 MYA but before the split of the three Papaveraceae species used in this study at ∼77 MYA. The phthalideisoquinoline noscapine and morphinan class of BIAs are exclusive to the opium poppy lineage. Ks estimation of paralogous pairs indicates that morphine biosynthesis evolved more recently than 18 MYA in the Papaver genus. In the preceding 100 million years gene duplication, neofunctionalization and recruitment of additional enzyme classes, combined with gene clustering, gene fusion, and gene amplification, resulted in emergence of medicinally valuable BIAs including morphine and noscapine.



中文翻译:

超过 1 亿年的酶进化支持罂粟科开花植物中吗啡的生产。

对来自开花植物毛茛目和蛋白质目的五种苄基异喹啉生物碱 (BIA) 生产物种的全基因组序列进行系统发育分析,揭示了导致这些化合物多样化的进化事件的顺序和时间。()-网状番荔枝碱是合成许多 BIA 的关键中间体,我们的分析揭示了这两个订单之间的平行演化,它们在大约 1.22 亿年前 (MYA) 出现分歧。小檗碱存在于整个毛茛纲的物种中,我们发现了对原始小檗碱类产生必不可少的基因的共同进化。苯并菲啶类,包括抗微生物化合物血根碱,是毛茛科罂粟科特有的,生物合成基因是在与毛茛科 110 MYA 分裂后出现的,但在本研究中使用的三种罂粟科物种在 77 年分裂之前出现米亚。邻苯二酚异喹啉那可品和吗啡喃类 BIA 是罂粟谱系独有的。ķ小号旁系同源对的估计表明吗啡生物合成比罂粟属中的 18 MYA 进化得更近。在之前的 1 亿年中,基因复制、新功能化和额外酶类的募集,加上基因聚类、基因融合和基因扩增,导致出现了具有药用价值的 BIA,包括吗啡和那可品。

更新日期:2020-02-05
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