Amaryllidaceae Alkaloids and Isoquinoline Alkaloids: A Perspective on Historical Approaches to Pathway Elucidation
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Alkaloids are among the most important secondary metabolites, and the discovery of their biosynthetic pathways is a key focus for pharmacological applications. Nowadays, these discoveries rely heavily on data from genomes, transcriptomes, and metabolomes. Since the 2000s, RNA sequencing has become a common approach for uncovering metabolic pathways by correlating plant transcript expression with metabolomic profiling. While the biosynthesis routes for isoquinoline alkaloids (IsAs) are well-documented in the literature, those for Amaryllidaceae alkaloids (AmAs) remain poorly described. In this review, we compile the available information on the genomic and transcriptomic approaches used in plants producing IsAs and AmAs and explore how the similarities between these two groups contribute to understanding the current challenges in elucidating AmAs pathways. Additionally, we compare historical approaches to discovering IsAs and AmAs pathways by analyzing key representatives—lycorine and galanthamine (AmAs) and morphine (IsAs)—while highlighting the role of various enzyme families involved in the synthesis of these alkaloids.