Insights into angiosperm evolution and lineage-specialized lignan biosynthesis from the early-diverging Schisandra genome

Abstract

Schisandraceae, an early-diverging angiosperm lineage, produces dibenzocyclooctadiene (DBCOD) lignans, unique bioactive compounds with liver-protecting properties. Although DBCOD lignan chemodiversity is well documented, their biosynthesis and evolution remain unclear. Here, we present a high-quality Schisandra chinensis genome, completing genomic representation of early angiosperms. Phylogenetic analysis confirms Austrobaileyales as sister to monocots, magnoliids, and eudicots, clarifying their evolutionary position. We identified an Austrobaileyales-specific whole-genome duplication postdiversification from Amborellales and Nymphaeales. Integrating coexpression networks and biochemical assays, we delineated five key steps in DBCOD lignan biosynthesis, including dimerization, hydroxylation, methylation, and C̶C phenol coupling. Notably, we found SchCYP719G1b, a previously unidentified enzyme catalyzing C̶C linkage to form the signature DBCOD scaffold. Substrate selectivity assays and quantum mechanical/molecular mechanics calculations suggested that the para-hydroxyl diradical electronic properties preferentially drive selective C2̶C2′ coupling over alternative pathways. Our findings illuminate early angiosperm evolution and the molecular basis of specialized lignan diversity.