Biosynthesis of quinolizidine alkaloids in lupins: mechanistic considerations and prospects for pathway elucidation

Covering: up to 2022Quinolizidine alkaloids (QAs) are a class of alkaloids that accumulate in a variety of leguminous plants and have applications in the agricultural, pharmaceutical and chemical industries. QAs are notoriously present in cultivated lupins (Lupinus spp.) where they complicate the use of the valuable, high-protein beans due to their toxic properties and bitter taste. Compared to many other alkaloid classes, the biosynthesis of QAs is poorly understood, with only the two first pathway enzymes having been discovered so far. In this article, we review the different biosynthetic hypotheses that have been put forth in the literature (1988-2009) and highlight one particular hypothesis (1988) that agrees with the often ignored precursor feeding studies (1964-1994). Our focus is on the biosynthesis of the simple tetracyclic QA (-)-sparteine, from which many of the QAs found in lupins derive. We examine every pathway step on the way to (-)-sparteine and discuss plausible mechanisms, altogether proposing the involvement of 6-9 enzymes. Together with the new resources for gene discovery developed for lupins in the past few years, this review will contribute to the full elucidation of the QA pathway, including the identification and characterization of the missing pathway enzymes.