Asperosaponin VI (ASA VI), the primary bioactive triterpenoid saponin marker of Dipsacus asper Wall. (Chinese Pharmacopoeia 2020), possesses significant neuroprotective, anti-inflammatory, and osteogenic activities. However, its low natural abundance limits large-scale production. In this study, we reported the first complete biosynthetic reconstruction of ASA VI in Saccharomyces cerevisiae using a modular synthetic biology strategy. The pathway included in situ UDP-arabinose (UDP-Ara) biosynthesis via heterologous expression of AtUGDH3, GuUXS2, and GuUXE1; triterpenoid scaffold generation through ERG9, ERG1, CqBAS1, and CqCYP716A78 for oleanolic acid (OA) production; and downstream modifications including C-23 hydroxylation by multicopy-expressed CaCYP714E19, stepwise glucosylation at C-28 by CaUGT73AD1 and CaUGT73C8, and C-3 arabinosylation by AsUGT99D1 to yield ASA VI. LC-MS analysis confirmed ASA VI biosynthesis and the accumulation of key intermediates (OA, HED, HED-28-Glc, and HED-28-Glc-Glc). Although production remained at trace levels (395 ng/L), pathway analysis suggested that the downstream glycosylation steps and UDP-Ara supply could be the major rate-limiting factors. This work established a microbial chassis for the sustainable synthesis of ASA VI and related arabinosylated saponins.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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