Catharanthus terpenoid indole alkaloids: biosynthesis and regulation
Catharanthus terpenoid indole alkaloids: biosynthesis and regulation
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DOI：
10.1007/s11101-006-9047-8
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发表时间：
2007-07-01
影响因子：
7.7
通讯作者：
Verpoorte, Rob
中科院分区：
文献类型：
--
作者：
El-Sayed, Magdi;Verpoorte, Rob
长春花属植物仍然是强效抗癌药物长春花碱和长春新碱的唯一来源。这种植物中的其他一些药物化合物，如阿玛利辛和蛇纹石也具有重要的经济价值。尽管玫瑰花已经得到了广泛的研究，并发表了大量的文献，但对其生物碱途径的全面表征尚未实现。在这里，我们回顾了最近在这个工厂上所做的一些工作。大部分工作集中在该途径的早期步骤，特别是发现了通向萜类化合物的2-C-甲基-D-赤藓糖醇4-磷酸(MEP)途径。甲氧戊酸和MEP途径都被植物利用，它们之间在不同的隔室之间存在明显的串扰。许多长春花生物碱途径早期的基因已经被克隆和过度表达，以促进其生物合成。对该途径后期步骤的研究导致了几个基因的克隆。讨论了吲哚生物碱生物合成所涉及的酶和基因，以及它们的定位和调控的各个方面。在生物碱监管层面已经取得了很大进展。饲养前体、生长调节剂处理和代谢工程是提高萜类吲哚生物碱生产率的良好工具。但我们对长春花生物碱途径的后期步骤和涉及的基因的了解仍然有限。
Catharanthus roseus is still the only source for the powerful antitumour drugs vinblastine and vincristine. Some other pharmaceutical compounds from this plant, ajmalicine and serpentine are also of economical importance. Although C. roseus has been studied extensively and was subject of numerous publications, a full characterization of its alkaloid pathway is not yet achieved. Here we review some of the recent work done on this plant. Most of the work focussed on early steps of the pathway, particularly the discovery of the 2-C-methyl-D-erythritol 4-phosphate (MEP)-pathway leading to terpenoids. Both mevalonate and MEP pathways are utilized by plants with apparent cross-talk between them across different compartments. Many genes of the early steps in Catharanthus alkaloid pathway have been cloned and overexpressed to improve the biosynthesis. Research on the late steps in the pathway resulted in cloning of several genes. Enzymes and genes involved in indole alkaloid biosynthesis and various aspects of their localization and regulation are discussed. Much progress has been made at alkaloid regulatory level. Feeding precursors, growth regulators treatments and metabolic engineering are good tools to increase productivity of terpenoid indole alkaloids. But still our knowledge of the late steps in the Catharanthus alkaloid pathway and the genes involved is limited.