Securing securinine: the biosynthesis of a unique tetracyclic alkaloid Catharine Wood, Benjamin Lichman, William Unsworth University of York, UK Alkaloids are a huge group of naturally occurring organic compounds which contain at least one nitrogen atom. They have numerous uses in daily life, ranging from food and drink to drugs and anaesthetics. Common alkaloids include morphine, an analgesic from opium poppy, nicotine from the tobacco plant and a well-known-often- consumed alkaloid, caffeine derived from over thirty plant species. The plant Flueggea suffruticosa is one of fifty fundamental herbs used in traditional Chinese medicines. Securinine is the active alkaloid associated with these medicinal properties, it is an effective GABAA antagonist and more recently has been studied for a broad spectrum of bioactivities that include neuroprotection and anticancer. Despite its extensive applications, the biosynthetic pathway for the majority of alkaloids, including securinine, is yet to be elucidated. By understanding how plants make these indispensable compounds, it will not only offer us direct access to the alkaloids themselves, but also the enzymes involved in their biosynthesis can be used as biocatalysts in synthetic chemistry to create novel compounds useful for the pharmaceutical industry. In this study, we combine transcriptomics and metabolomics of F.suffruticosa to identify candidate genes involved in securinine biosynthesis, once identified we cloned these genes into Escherichia coli expression vectors for protein purification and conducted enzyme activity assays using HPLC-MS to test our hypothesis. Alongside this, we chemically synthesised the putative precursors to securinine, which we will test with plant extract to determine the transformations leading to this valuable compound. We aim to elucidate the biosynthetic pathway for tetracyclic alkaloids in F.suffruticosa , a novel pathway and identify stereoselective biocatalysts capable of synthesising complex compounds. References 1. Antien, K., Lacambra, A., Cossío, F.P., Massip, S., Deffieux, D., Pouységu, L., Peixoto, P.A. and Quideau, S., 2019. Bio- inspired Total Synthesis of Twelve Securinega Alkaloids: Structural Reassignments of (+)-Virosine B and (−)-Episecurinol A.Chemistry–A European Journal,25(49), pp.11574-11580. 2. Sankawa, U., Ebizuka, Y. and Yamasaki, K., 1977. Biosynthesis of securinine, the main alkaloid of Securinega suffruticosa. Phytochemistry,16(5), pp.561-563.
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