ArticleNature plants2026
Elucidation of gene clusters underlying withanolide biosynthesis in ashwagandha through yeast metabolic engineering.
Article in Nature plants, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Advances in molecular breeding of medicinal plants.Molecular horticulture · 2026Review
- Chemically guided single-cell transcriptomics reveals sulfotransferase-mediated scaffold remodeling in securinine biosynthesis.Nature communications · 2026Article
- Neural Spectral Prediction for Structure Elucidation with Tandem Mass Spectrometry.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
9 authors.
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Abstract
Withanolides are medicinally important steroidal lactones produced by Withania somnifera (ashwagandha), among other Solanaceae family plants, known for their neurological, anti-cancer and adaptogenic properties. However, the biosynthetic pathway to withanolides is largely unknown, preventing scale-up and hindering pharmaceutical applications. Here we generate a chromosome-scale assembly of the W. somnifera genome and identify two withanolide biosynthetic gene clusters that exhibit a segmented tissue-specific expression pattern. Using metabolic engineering in yeast, complemented by heterologous expression in Nicotiana benthamiana and virus-induced gene silencing in W. somnifera, we elucidate the withanolide biosynthetic pathway to an intermediate with all characteristic chemical features of withanolides. We report two cytochrome P450s (CYP87G1 and CYP749B2) and a short-chain dehydrogenase (SDH2) responsible for lactone ring formation. We additionally discover two P450s (CYP88C7 and CYP88C10) and a sulfotransferase (SULF1) that generate the characteristic A-ring structure of withanolides, featuring a C-1 ketone and C-2-C-3 unsaturation. Identifying SULF1 as a core pathway enzyme challenges the conventional paradigm of sulfotransferases as tailoring enzymes and suggests a wider role for this enzyme family in plant specialized metabolism. This work opens new avenues for the sustainable production of withanolides through biomanufacturing and for drug development leveraging the withanolide scaffold.
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