Lysine-derived Alkaloids: Overview and Update on Biosynthesis and Medicinal Applications with Emphasis on Quinolizidine Alkaloids

Background: Plants produce a vast variety of specialized metabolites which can be a rich source for lead compounds for the development of new drugs. Alkaloids are one the largest groups of plant specialized metabolites important for natural product based pharmaceuticals. Of these, lysine (Lys)-derived alkaloids exhibit a wide range of pharmacological properties which are beneficial for humans. For instance they have anticancer, anti-Alzheimer’s disease, anti-inflammatory, hypocholesterolemic and antiarrhtymic effects. Lys-derived alkaloids are widely distributed throughout the plant kingdom: they can be found in various species from clubmosses to flowering plants. Lys is one of the most essential amino acids for humans and livestock and is synthesized in the plastids of land plants. Lys-derived alkaloids can be divided into four major groups including quinolizidine, lycopodium, piperidine, and indolizidine alkaloids. Despite the importance of these compounds, the biosynthetic pathways of Lys-derived alkaloids are not well understood. With the exception of indolizidine alkaloids, Lys decarboxylase (LDC) is the enzyme involved in the first committed step of the biosynthesis by catalyzing the transformation of L-Lys into cadaverine. Cadaverine is then oxidized by copper amine oxidase (CuAO) and spontaneously cyclized to Δ1-piperideine Schiff base which is a universal intermediate for the production of various Lys-derived alkaloids. Keywords: Anabasine, indolizidine alkaloids, Lycopodium alkaloids, lysine-derived alkaloids, piperidine alkaloids, plastidderived alkaloids, quinolizidine alkaloids.