Nonsymmetric formation of Δ ¹ -piperideine from lysine in plants via a bacterial-like PLP-dependent enzyme

Piperidine alkaloids in plants derive from lysine via Δ ¹ -piperideine. We investigated the alkaloid biosynthesis in Flueggea suffruticosa , a plant that produces diverse piperidine alkaloids, including securinine. Until now, pathways leading to the formation of Δ ¹ -piperideine have involved two enzymatic steps: a decarboxylase and an oxidase, proceeding via free cadaverine. We discovered Δ ¹ -piperideine synthase (PS), a PLP-dependent enzyme that forms Δ ¹ -piperideine directly from lysine via an oxidative deamination. We demonstrate that PS catalyses this transformation in a non-symmetric manner, and show it is positioned within the group III decarboxylase family, which is typically associated with prokaryotes. We also identified a paralog gene exhibiting decarboxylase activity. This work delineates the first enzymatic step in the biosynthesis of securinine as an unprecedented oxidative deamination of lysine. It also marks the identification of the first eukaryotic group III decarboxylase and resolves the longstanding question of non-symmetric nitrogen incorporation in piperidine alkaloids.