Complete biosynthetic pathway of furochromones and its evolutionary mechanism in Apiaceae plants

Furochromones are bioactive and specific secondary metabolites of many Apiaceae plants. Their biosynthesis remains largely unexplored. In this work, we dissected the complete biosynthetic pathway of major furochromones in the medicinal plant Saposhnikovia divaricata by characterizing novel prenyltransferase, peucenin cyclase, methyltransferase, hydroxylase, and glycosyltransferases. De novo biosynthesis of prim-O-glucosylcimifugin and 5-O-methylvisamminoside was then realized in tobacco leaves. Through comparative genomic and transcriptomic analyses, we further found that proximal duplication and high expression of a pentaketide chromone synthase gene SdPCS, together with the presence of a lineage-specific peucenin cyclase gene SdPC, led to the predominant accumulation of furochromones in the roots of S. divaricata among surveyed Apiaceae plants. This study paves the way for metabolic engineering production of furochromones, and sheds light into evolutionary mechanism of furochromone biosynthesis among Apiaceae plants.