ArticleNature communications2025
Gymnosperm-specific CYP90Js enable biflavonoid biosynthesis and microbial production of amentoflavone.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Structural insights into the structure-activity relationships of flavonoids targeting WSSV and LvGSTMu.Molecular diversity · 2026Article
- Patterns of Biflavonoid Accumulation in Ginkgo (Plants (Basel, Switzerland) · 2026Article
- DcMYB5 transcription factor regulates the biosynthesis of diosgenin by directly repressing CYP90B gene expression in Dioscorea composita.Plant cell reports · 2026Article
- Synthetic Strategies and Biological Diversity of Biflavonoids: Current Status and Perspective.Molecules (Basel, Switzerland) · 2026Review
- Bacterial cytochrome P450 for oxidative halogenated biaryl coupling.ACS catalysis · 2026Article
- Dimerized Power: The Antimicrobial and Antiviral Promise of Biflavonoids.Biomolecules · 2025Review
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Authors and funding
6 authors.
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Abstract
Biflavonoids, a unique subclass of flavonoids with superior clinical activity compared to their monomeric counterparts, offer distinct therapeutic benefits by targeting multiple pathways in neurodegenerative disorders. However, the mechanism of flavonoid dimerization in plants remains enigmatic. Here, we identify CYP90J orthologs as the missing link in biflavonoid biosynthesis. We demonstrate that gymnosperm-specific CYP90Js catalyze intermolecular C-C bond formation in the biosynthesis of biaryl natural products. Together with the identified O-methyltransferases, CYP90Js are responsible for the production of ginkgo biflavonoids. Phylogenetic analysis reveals that the CYP90J subfamily evolved from CYP90E of lycophytes and is found exclusively in gymnosperms. Molecular dynamics simulations show that regioselective dimerization of apigenin to amentoflavone is driven by spatial constraints and π-π stacking interactions. QM/MM calculations support a heme-induced diradical coupling mechanism. Notably, the de novo reconstruction of amentoflavone was achieved in an engineered L-tyrosine E. coli strain, with a titer of 4.75 mg/L. Overall, the discovery of CYP90Js represents a crucial step toward understanding flavone dimerization, and the engineering of biflavonoids in microorganism provides a promising biotechnology platform for expanding therapeutic applications of biflavonoids.
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