Insights into angiosperm evolution and lineage-specialized lignan biosynthesis from the early-diverging <i>Schisandra</i> 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 <i>Schisandra chinensis</i> 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 C─C phenol coupling. Notably, we found SchCYP719G1b, a previously unidentified enzyme catalyzing C─C linkage to form the signature DBCOD scaffold. Substrate selectivity assays and quantum mechanical/molecular mechanics calculations suggested that the <i>para</i>-hydroxyl diradical electronic properties preferentially drive selective C2─C2' coupling over alternative pathways. Our findings illuminate early angiosperm evolution and the molecular basis of specialized lignan diversity.