Metabolic Pathway Design for Lycorine Biosynthesis Via an in silico Approach

The Amaryllidaceae family includes a wide group of alkaloid-producing plants, which have been extensively studied for presenting cytotoxic, anti-tumor, antiplasmodial, antiviral effects, among others; becoming a target of pharmaceutical interest. Previous studies have reported the presence of lycorine, an alkaloid with broad antiviral activity, in the Amaryllidaceae species, Hymenocallis littoralis, native to South America and present in Colombia. However, the synthesis of alkaloids in plants is very low, which hinders their industrial production. A strategy to overcome this is through metabolic engineering in recombinant organisms, but these technologies require knowledge of the biosynthetic pathways of the molecules. Despite the importance of these natural products, there are few enzymes and genes reported to date for this family. Additionally, studies of the Amaryllidaceae family have been carried out on Eurasian species, such as Narcissus and Lycoris radiata, and very little is known about the species present in the neotropics, such as H. littoralis, which have great potential to generate medicinal products and represent an attribute for the development of the country by taking advantage of its biodiversity. Due to the above, this project aimed to reconstruct in silico a possible biosynthetic pathway of lycorine from known databases of different organisms, using a two-step algorithm, which identifies both the optimum overall stoichiometry (optStoic) and selects the shortest biosynthetic pathway in terms of thermodynamic viability. In the future, these results will be implemented in a recombinant organism for lycorine production.