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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Homolog of tocopherol C methyltransferases catalyzes N methylation in anticancer alkaloid biosynthesis
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Homolog of tocopherol C methyltransferases catalyzes N methylation in anticancer alkaloid biosynthesis

机译：生育酚C甲基转移酶的同系物在抗癌生物碱生物合成中催化N甲基化

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摘要

Madagascar periwinkle (Catharanthus roseus) is the sole source of the anticancer drugs vinblastine and vincristine, bisindole alkaloids derived from the dimerization of the terpenoid indole alkaloids vindoline and catharanthine. Full elucidation of the biosynthetic pathways of these compounds is a prerequisite for metabolic engineering efforts that will improve production of these costly molecules. However, despite the medical and commercial impor tance of these natural products, the biosynthetic pathways remain poorly understood. Here we report the identification and charac terization of a C. roseus cDNA encoding an 5-adenosyl-L-methio nine-dependent N methyltransferase that catalyzes a nitrogen methylation involved in vindoline biosynthesis. Recombinant enzyme produced in Escherichia coli is highly substrate specific, displaying a strict requirement for a 2,3-dihydro bond in the aspi dosperma skeleton. The corresponding gene transcript is induced in methyl jasmonate-elicited seedlings, along with the other known vindoline biosynthetic transcripts. Intriguingly, this unique N methyltransferase is most similar at the amino acid level to the plastidic γ-tocopherol C methyltransferases of vitamin E biosynth esis, suggesting an evolutionary link between these two function ally disparate methyltransferases.
机译：马达加斯加长春花（Catharanthus roseus）是长春新碱和长春新碱的抗癌药的唯一来源，长春新碱和长春新碱是从萜类吲哚生物碱长春花碱和长春花碱的二聚作用而获得的双吲哚生物碱。充分阐明这些化合物的生物合成途径是代谢工程工作的先决条件，这将改善这些昂贵分子的生产。然而，尽管这些天然产物的医学和商业重要性，但对生物合成途径的了解仍然很少。在这里，我们报告鉴定和编码编码5-伏特基-L-甲基10-依赖性N甲基转移酶，催化与长春花碱生物合成有关的氮甲基化的玫瑰C.roseus cDNA。大肠杆菌中产生的重组酶具有高度的底物特异性，显示了对甜菜皮中的2,3-二氢键的严格要求。茉莉酸甲酯诱导的幼苗中诱导了相应的基因转录本，以及其他已知的长春花碱生物合成转录本。有趣的是，这种独特的N甲基转移酶在氨基酸水平上与维生素E生物合成的质体γ-生育酚C甲基转移酶最为相似，表明这两种功能完全不同的甲基转移酶之间存在进化联系。

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