Genome evolution and glycosyltransferase diversification shape asperosaponin biosynthesis in Dipsacus asperoides

Deciphering the genomic and enzymatic features associated with high-abundance specialized metabolism is important for understanding and engineering bioactive natural product biosynthesis. Asperosaponin , a hederagenin-based saponin, accumulates at exceptionally high levels in Dipsacus asperoides roots and is by far the predominant triterpenoid saponin. Here, by integrating a chromosome-level genome assembly with comparative genomics, transcriptomics, metabolite profiling, and biochemical characterization, we reconstructed a major biosynthetic route to asperosaponin and identified diversification of triterpenoid-associated gene families. Functional analyses revealed an ordered glycosylation sequence in which DaUGT73GZ2 preferentially accepts C-3-glycosylated substrates retaining a free C-28 carboxyl group, thereby establishing a C-3-before-C-28 glycosylation order during asperosaponin biosynthesis. Phylogenetic and biochemical analyses further uncovered functional differentiation among UGT85CA enzymes involved in C-3 arabinosylation, while genomic and expression analyses revealed lineage-specific patterns of pathway gene duplication and transcriptional regulation. Together, these findings identify genomic, enzymatic, and transcriptional features associated with the distinctive, high-abundance triterpenoid saponin profile of D. asperoides roots and provide a framework for understanding and engineering triterpenoid saponin biosynthesis.

Yang, R., Fu, C., Zhao, X., Zhao, Y., Huang, W., Li, M., Xiang, G., Xiong, J., Wang, Y., Chen, G., Liu, Q., Yang, S., Zhang, G., He, S., Liang, Y.

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