Molecular basis of the biosynthesis of pharmacologically active alkaloids from Carolina Jasmine

卡罗莱纳茉莉药理活性生物碱生物合成的分子基础

• 批准号: 286056487
• 负责人: Professor Dr. Jakob Franke
• 金额: --
• 依托单位: Zentrum für Biomolekulare Wirkstoffe (BMWZ)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/286056487?language=en
• 关键词: Molecular; basis; biosynthesis; pharmacologically; active

Plants have been used by mankind for thousands of years due to their ability to produce highly varied and medicinally relevant secondary metabolites. However, the industrial production of such natural products is often highly laborious, requires vast cultivation areas and suffers from fluctuating production conditions. This dilemma has also hampered the use of a group of natural products from Carolina Jasmine (Gelsemium sempervirens), which are systematically named oxindole alkaloids. These compounds exhibit antitumoral, anti-inflammatory, analgesic and anxiolytic activities, but their low production rates in the plant severely limit their application. Additionally, their complex structures prevent efficient synthetic routes. A promising alternative would be the biotechnological production of these compounds by microorganisms, however, this requires a thorough understanding of the underlying biosynthetic pathway of these compounds. Accordingly, the aim of this research project is the elucidation of the biosynthetic steps leading to the oxindole alkaloids in G. sempervirens. This information can then be later translated to microbial biotechnology systems aimed at the increased production of these unique compounds. To begin with, biosynthetic genes will be identified based on sequence data of the plant genome and transcriptome. Relevant gene products will then be characterized in the plant using virus-induced gene silencing and by production in microbial model organisms, which will give further mechanistic insights of unusual transformations. Additionally, the localization of involved genes and enzymes will be assessed, for example by hybridization techniques or using fluorescence microscopy, to provide a better understanding of the spatial organization of the biosynthetic pathway. All of these methods have been established in various plants in recent years, so that the biosynthesis of the Gelsemium alkaloids can now be studied for the first time with modern methodology. In conclusion, these studies are not only important for a better understanding of the function and organization of the oxindole biosynthetic pathway in G. sempervirens, but also as a basis for future biotechnological applications to harness the pharmacological potential of these alkaloids.

由于植物能够产生高度多样化且具有药用相关性的次生代谢物，植物已被人类使用了数千年。然而，此类天然产品的工业生产往往非常费力，需要广阔的种植面积，并且生产条件波动较大。这种困境也阻碍了来自卡罗莱纳茉莉（Gelsemium sempervirens）的一组天然产物的使用，这些天然产物被系统地命名为羟吲哚生物碱。这些化合物表现出抗肿瘤、抗炎、镇痛和抗焦虑活性，但它们在植物中的低生产率严重限制了它们的应用。此外，它们复杂的结构阻碍了有效的合成路线。一个有前途的替代方案是通过微生物生物技术生产这些化合物，然而，这需要彻底了解这些化合物的潜在生物合成途径。因此，该研究项目的目的是阐明G. sempervirens 中产生羟吲哚生物碱的生物合成步骤。这些信息随后可以转化为微生物生物技术系统，旨在增加这些独特化合物的产量。首先，将根据植物基因组和转录组的序列数据来鉴定生物合成基因。然后，将使用病毒诱导的基因沉默和微生物模型生物体中的生产来表征植物中的相关基因产物，这将为异常转化提供进一步的机制见解。此外，还将评估所涉及基因和酶的定位，例如通过杂交技术或使用荧光显微镜，以更好地理解生物合成途径的空间组织。近年来，所有这些方法都已在各种植物中建立，因此现在可以首次用现代方法研究钩吻生物碱的生物合成。总之，这些研究不仅对于更好地了解永久绿地霉中羟吲哚生物合成途径的功能和组织具有重要意义，而且还为未来利用这些生物碱的药理学潜力的生物技术应用奠定了基础。