Lineage‐Specific CYP80 Expansion and Benzylisoquinoline Alkaloid Diversity in Early‐Diverging Eudicots

Abstract

Abstract Menispermaceae species, as early‐diverging eudicots, can synthesize valuable benzylisoquinoline alkaloids (BIAs) like bisbenzylisoquinoline alkaloids (bisBIAs) and sinomenines with a wide range of structural diversity. However, the evolutionary mechanisms responsible for their chemo‐diversity are not well understood. Here, a chromosome‐level genome assembly of Menispermum dauricum is presented and demonstrated the occurrence of two whole genome duplication (WGD) events that are shared by Ranunculales and specific to Menispermum, providing a model for understanding chromosomal evolution in early‐diverging eudicots. The biosynthetic pathway for diverse BIAs in M. dauricum is reconstructed by analyzing the transcriptome and metabolome. Additionally, five catalytic enzymes – one norcoclaurine synthase (NCS) and four cytochrome P450 monooxygenases (CYP450s) – from M. dauricum are responsible for the formation of the skeleton, hydroxylated modification, and C‐O/C‐C phenol coupling of BIAs. Notably, a novel leaf‐specific MdCYP80G10 enzyme that catalyzes C2′‐C4a phenol coupling of (S)‐reticuline into sinoacutine, the enantiomer of morphinan compounds, with predictable stereospecificity is discovered. Moreover, it is found that Menispermum‐specific CYP80 gene expansion, as well as tissue‐specific expression, has driven BIA diversity in Menispermaceae as compared to other Ranunculales species. This study sheds light on WGD occurrences in early‐diverging eudicots and the evolution of diverse BIA biosynthesis.

Keywords

• benzylisoquinoline alkaloids
• biosynthetic pathway
• chemo‐diversity
• Menispermum
• stereospecificity