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Plant Communications：吗啡的前世今生～源起

已有 3368 次阅读 2020-2-13 06:02 |个人分类:每日摘要|系统分类:论文交流

Over 100 million years of enzyme evolution underpinning the production of morphine in the Papaveraceae family of flowering plants

First author: Yi Li; Affiliations: University of York (约克大学): York, UK

Corresponding author: Ian A. Graham

Phylogenetic gene tree analysis of whole genomes from 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 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, are 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 indicate that morphine biosynthesis evolved more recently than 18 MYA in the Papaver genus. In the preceeding 100 MY gene duplication, neofunctionalisation 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.

Ranunculales：orange；Papaveraceae：light green；opium poppy：dark green.

本文中，作者通过对来自开花植物的两个目：毛茛目和山龙眼目中能够产生苄基异喹啉生物碱（BIA）的五个物种进行了全基因组的系统发育基因树构建，揭示了导致这些化合物分化的演化事件发生的时间与相关的序列。(S)-Reticuline是合成许多种BIAs的中间产物，作者的分析发现在这两个目虽然在122个百万年前就已经分化，但他们之间存在平行演化。小檗碱（berberine）在所有的毛茛目物种中都有发现，作者发现原小檗碱类化合物生物合成相关的基因存在共同演化。包括抗菌化合物血根碱（sanguinarine）在内的苯并菲啶（benzophenanthridine）类化合物只在毛茛目中的罂粟科植物中存在，并且这类化合物生物合成相关的基因是在罂粟科与毛茛科植物分化之后（~110Mya）、罂粟科中三个植物物种分化之前（~77Mya）出现的。那可丁（noscapine）是一种苯酞异喹啉类（phthalideisoquinoline）生物碱，其与吗啡喃（morphinan）一样都是鸦片罂粟支系植物中特有的一类BIAs。旁系同源基因的Ks估计显示罂粟属植物中吗啡生物合成可能是18Mya之后才演化形成的。因此，100Mya左右的基因复制、新功能化以及额外酶的招募与基因聚集、基因融合以及基因扩增共同导致了包括吗啡和那可丁等具有较高医用价值的BIAs化合物的出现。