Phylogenomic elucidation of withanolide biosynthesis in Nightshade plants

茄属植物中茄内酯生物合成的系统发育学阐明

• 批准号: 516566273
• 负责人: Professor Dr. Jakob Franke
• 金额: --
• 依托单位: Institut für Pflanzenbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/516566273?language=en
• 关键词: Phylogenomic; elucidation; withanolide; biosynthesis; Nightshade

Withanolides are specialised metabolites from Nightshade plants with potent antiproliferative activity, which possess a long history of human usage as traditional medicine. More than 700 natural withanolides have been isolated so far, and many representatives are biologically active. Little is known, however, how these structurally diverse steroidal lactones are synthesised in plants. In preliminary work, we identified a putative withanolide biosynthetic gene cluster by analysis of all publicly available genome and transcriptome data of withanolide producers. In this project, building on a collaboration between a plant biochemistry group and a bioinformatics group, we want to explore this hypothesis and leverage it for the phylogenomic elucidation of withanolide biosynthesis. Specifically, we will verify our already identified gene candidates by heterologous expression and virus-induced gene silencing. In addition, to further understand the evolution of different withanolide subclasses, we will sequence three additional genomes of the withanolide producers Withania somnifera, Datura innoxia and Nicandra physalodes. From this sequence data, we will select and evaluate gene candidates based on synteny, phylogenetic relationship, and co-expression that might be responsible for the generation of structural subclasses. Based on the sequence data and the biosynthetic genes gained by this approach, we will then be able to reconstruct the evolutionary history of withanolides and their different subclasses. Thus, our project will provide fundamental insights into the molecular basis and evolution of withanolide biosynthesis. On a long term, these findings will help to better harness the medicinal properties of this structurally varied natural product class for drug development.

龙葵内酯是龙葵属植物中具有抗肿瘤活性的特殊代谢产物，作为传统药物在人类中有着悠久的应用历史。迄今为止，已分离出700多种天然睡茄内酯，其中许多代表性化合物具有生物活性。然而，很少有人知道这些结构不同的甾体内酯是如何在植物中合成的。在初步工作中，我们通过分析所有公开的withanesthetic生产者的基因组和转录组数据，确定了一个推定的withanesthetic生物合成基因簇。在这个项目中，建立在植物生物化学组和生物信息学组之间的合作，我们希望探索这一假设，并利用它来阐明withanesthetic生物合成的基因组。具体来说，我们将通过异源表达和病毒诱导的基因沉默来验证我们已经确定的候选基因。此外，为了进一步了解不同withanesthetic亚类的进化，我们将测序withanesthetic生产者Withania somnifera，Datura innoxia和Nicandra physalodes的另外三个基因组。从这个序列数据，我们将选择和评估基因候选人的基础上同线性，系统发育关系，共表达，可能是负责产生的结构子类。基于序列数据和通过这种方法获得的生物合成基因，我们将能够重建睡茄内酯及其不同子类的进化历史。因此，我们的项目将提供基本的见解的分子基础和进化的withanesthetic生物合成。从长远来看，这些发现将有助于更好地利用这种结构多样的天然产物的药用特性进行药物开发。