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.