The genetic basis for the production of toxic quinolizidine alkaloids in lupins.

Lupins (Lupinus spp.) are promising protein crops that accumulate bitter and toxic quinolizidine alkaloids (QAs). The effective removal of QAs through new breeding technologies is hampered by a poor understanding of their biosynthesis. In this study, we used pathway reconstruction and mutant analysis to elucidate the full QA pathway in L. angustifolius [narrow-leafed lupin (NLL)] comprising 15 enzymatic steps. Major latex protein-like proteins play a prominent role in the pathway by accelerating spontaneous chemical equilibria, and an oxidoreductase-like protein ensures stereoselectivity. We also engineered a new low-alkaloid NLL line and identified the causal mutation in an existing low-alkaloid line of L. albus. Our work reveals the genetic and biochemical basis of toxic QA production and streamlines the de novo domestication of wild lupins and other QA-containing legumes.