van Der Heijden Robert, Jacobs Denise I, Snoeijer Wim, Hallard Didier, Verpoorte Robert
Division of Pharmacognosy, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Curr Med Chem. 2004 Mar;11(5):607-28. doi: 10.2174/0929867043455846.
The Catharanthus (or Vinca) alkaloids comprise a group of about 130 terpenoid indole alkaloids. Vinblastine is now marketed for more than 40 years as an anticancer drug and became a true lead compound for drug development. Due to the pharmaceutical importance and the low content in the plant of vinblastine and the related alkaloid vincristine, Catharanthus roseus became one of the best-studied medicinal plants. Consequently it developed as a model system for biotechnological studies on plant secondary metabolism. The aim of this review is to acquaint a broader audience with the recent progress in this research and with its exciting perspectives. The pharmacognostical aspects of the Catharanthus alkaloids cover botanical (including some historical), phytochemical and analytical data. An up-to-date view on the biosynthesis of the alkaloids is given. The pharmacological aspects of these alkaloids and their semi-synthetic derivatives are only discussed briefly. The biotechnological part focuses on alternative production systems for these alkaloids, for example by in vitro culture of C. roseus cells. Subsequently it will be discussed to what extent the alkaloid biosynthetic pathway can be manipulated genetically ("metabolic engineering"), aiming at higher production levels of the alkaloids. Another approach is to produce the alkaloids (or their precursors) in other organisms such as yeast. Despite the availability of only a limited number of biosynthetic genes, the research on C. roseus has already led to a broad scientific spin-off. It is clear that many interesting results can be expected when more genes become available.
长春花生物碱包含约130种萜类吲哚生物碱。长春碱作为一种抗癌药物已上市40多年，成为药物研发中真正的先导化合物。由于长春碱及相关生物碱长春新碱在植物中的药用重要性及低含量，长春花成为研究最为深入的药用植物之一。因此，它发展成为植物次生代谢生物技术研究的模型系统。本综述旨在让更广泛的读者了解该研究的最新进展及其令人兴奋的前景。长春花生物碱的生药学方面涵盖植物学（包括一些历史）、植物化学和分析数据。给出了生物碱生物合成的最新观点。这些生物碱及其半合成衍生物的药理学方面仅作简要讨论。生物技术部分重点关注这些生物碱的替代生产系统，例如通过长春花细胞的体外培养。随后将讨论生物碱生物合成途径在多大程度上可以通过基因操作（“代谢工程”）来提高生物碱的产量。另一种方法是在其他生物体如酵母中生产生物碱（或其前体）。尽管仅可获得有限数量的生物合成基因，但对长春花的研究已经产生了广泛的科学衍生成果。显然，当有更多基因可用时，可以期待许多有趣的结果。
