ArticleNature communications2026
Discover the maze-like network for glabridin biosynthesis.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Characterization of two key cytochrome P450 enzymes inSynthetic and systems biotechnology · 2027Article
- An aromatic substrate prenyltransferase involved in the chemical diversification of flavonoids in Glycyrrhiza glabra.Planta · 2026Article
- Metabolic Engineering Strategies for Flavonoid Biosynthesis in Saccharomyces cerevisiae: Current Advances and Future Perspectives.Biotechnology and bioengineering · 2026Review
- Biosynthesis of Sciadonic Acid Derived from Gymnosperms with Anti-Colitis Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Discovery of an isoflavone biosynthetic pathway in Iridaceae plants.Nature communications · 2026Article
- Interactomics-driven discovery of alkaloid biosynthetic pathways in kratom.bioRxiv : the preprint server for biology · 2026Article
- Block-building with yeast to elucidate an artificial pathway for de novo biosynthesis of glabridin.Nature communications · 2026Article
- Design of the biosensor-dependent coupling system stabilizes the high-synthesis phenotype of cell factory.Nature communications · 2026Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Flavonoid diversity arises from modifications of a few precursors by tailored enzymes, yet the complexity of their evolved metabolic networks complicates pathway elucidation and design. Here, by combining chromosome-scale genome assembly with large-scale transcriptome analysis, we identify and reconstruct the glabridin biosynthetic pathway in yeast, enabling de novo production of this antioxidant flavonoid from Glycyrrhiza glabra L. By analyzing 183 licorice transcriptomes, we discover four classes of enzymes capable of modify isoflavan scaffolds. Among 13 theoretical routes, we validate six functional pathways, revealing a ladder-like, multi-route tailoring network. This network features a multi-step "protection-deprotection" mechanism driven by a dynamic methylation-demethylation cycle that regulate intermediate hydrophilicity and enzyme affinity, thereby enabling species-specific glabridin synthesis. Reconstruction of this network in yeast shows that metabolic redundancy and interconnectivity enhance robustness and yield compared to single-route designs. These results establish a biosynthetic paradigm with broad implications for natural product discovery and biomanufacturing.
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