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Abstract
Methyl jasmonate (MeJA) is a known elicitor of plant specialized metabolism, including triterpenoid saponins. Saponaria vaccaria is an annual herb used in traditional Chinese medicine, containing large quantities of oleanane-type triterpenoid saponins with anticancer properties and structural similarities to the vaccine adjuvant QS-21. Leveraging the MeJA-elicited saponin biosynthesis, we identify multiple enzymes catalyzing the oxidation and glycosylation of triterpenoids in S. vaccaria. This exploration is aided by Pacbio full-length transcriptome sequencing and gene expression analysis. A cellulose synthase-like enzyme can not only glucuronidate triterpenoid aglycones but also alter the product profile of a cytochrome P450 monooxygenase via preference for the aldehyde intermediate. Furthermore, the discovery of a UDP-glucose 4,6-dehydratase and a UDP-4-keto-6-deoxy-glucose reductase reveals the biosynthetic pathway for the rare nucleotide sugar UDP-d-fucose, a likely sugar donor for fucosylation of plant natural products. Our work enables the production and optimization of high-value saponins in microorganisms and plants through synthetic biology approaches.
Methyl jasmonate triggers saponin production in Saponaria vaccaria. Using transcriptome data and heterologous expression, the authors identify P450s and glycosyltransferases that modify triterpenoids. They also discover the pathway for UDP-D-fucose biosynthesis.
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1 University of California, Department of Plant and Microbial Biology, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878); Joint BioEnergy Institute, Emeryville, USA (GRID:grid.451372.6) (ISNI:0000 0004 0407 8980); Lawrence Berkeley National Laboratory, Environmental Genomics and Systems Biology Division, Berkeley, USA (GRID:grid.184769.5) (ISNI:0000 0001 2231 4551)
2 Joint BioEnergy Institute, Emeryville, USA (GRID:grid.451372.6) (ISNI:0000 0004 0407 8980); University of California, California Institute of Quantitative Biosciences (QB3), Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878)
3 University of California, Department of Plant and Microbial Biology, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878); Joint BioEnergy Institute, Emeryville, USA (GRID:grid.451372.6) (ISNI:0000 0004 0407 8980)
4 Joint BioEnergy Institute, Emeryville, USA (GRID:grid.451372.6) (ISNI:0000 0004 0407 8980); Lawrence Berkeley National Laboratory, Biological Systems and Engineering Division, Berkeley, USA (GRID:grid.184769.5) (ISNI:0000 0001 2231 4551)
5 Joint BioEnergy Institute, Emeryville, USA (GRID:grid.451372.6) (ISNI:0000 0004 0407 8980); University of California, California Institute of Quantitative Biosciences (QB3), Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878); University of California, Department of Chemical & Biomolecular Engineering, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878)
6 Joint BioEnergy Institute, Emeryville, USA (GRID:grid.451372.6) (ISNI:0000 0004 0407 8980); University of California, California Institute of Quantitative Biosciences (QB3), Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878); Lawrence Berkeley National Laboratory, Biological Systems and Engineering Division, Berkeley, USA (GRID:grid.184769.5) (ISNI:0000 0001 2231 4551); University of California, Department of Chemical & Biomolecular Engineering, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878); University of California, Department of Bioengineering, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878); Technical University of Denmark, Kongens Lyngby, Denmark (GRID:grid.5170.3) (ISNI:0000 0001 2181 8870); Shenzhen Institutes for Advanced Technologies, Center for Synthetic Biochemistry, Shenzhen, China (GRID:grid.458489.c) (ISNI:0000 0001 0483 7922)