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

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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.