Biosynthesis of alkaloids in Amaryllidaceae plants: a review

Amaryllidaceae alkaloids are a group of specialized metabolites found predominantly in the Amaryllidaceae plant family. Approximately 600 naturally occurring Amaryllidaceae alkaloids have been identified, many of which possess a variety of potent biological and pharmacological properties. However, only the Amaryllidaceae alkaloid galanthamine, an acetylcholinesterase inhibitor used to treat symptoms of neurodegenerative disorders such as Alzheimer's disease, is currently on the market. Despite promising pharmacological potential, the clinical development of Amaryllidaceae alkaloids is hindered by limited commercial availability. In contrast to the large body of knowledge on the pharmacological and phytochemical aspects of Amaryllidaceae alkaloids, their molecular and physiological features are less explored. A better understanding of Amaryllidaceae alkaloid biosynthesis and metabolic regulation is crucial to take advantage of new metabolic engineering technologies for improving the efficiency and sustainability of plant or microbial Amaryllidaceae alkaloid production. Although there is still much to learn, over the past several years comparative transcriptomic and traditional biochemical approaches have led to significant advances in the identification of the molecular players involved in producing Amaryllidaceae alkaloids including enzymes from the shikimate and phenylpropanoid pathways. The identity of few Amaryllidaceae alkaloid biosynthetic enzymes and several genes encoding them has been reported. In this review, an overview of the current knowledge on the biosynthesis of Amaryllidaceae alkaloids is presented.