ArticleNature communications2026
Complete biosynthesis of the clinical agent escin Ia.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Escin Ia is a barrigenol-type triterpenoid specific to Aesculus seeds and is widely utilized in clinical practice for the treatment of cerebral edema, swelling, and venous insufficiency. Here, we fully elucidated its biosynthetic pathway by identifying ten previously uncharacterized enzymes from Aesculus chinensis. AcCYP716BX1/2 catalyze the C-22α and C-28 hydroxylation of the β-amyrin scaffold, and AcCYP714E67 mediates the C-24 hydroxylation to produce protoaescigenin. Sequential glycosylation at the 2'-O and 4'-O positions is catalyzed by AcUGT94AK1/3/6 and AcUGT87AZ3, respectively, forming aesculuside B. AcCCL3 catalyzes the formation of tigloyl-CoA, and AcBAHD13/17 catalyze the C-21β tigloylation of aesculuside B to yield desacetylescin Ia. These enzymes significantly broaden the catalytic versatility of their respective gene families. Finally, we successfully reconstructed the complete pathway in Nicotiana benthamiana, enabling the heterologous production of escin Ia. This work fully elucidates the biosynthesis of escin Ia and establishes a foundation for the green production of barrigenol-type triterpenoid saponins.
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