ArticleNature communications2026
Block-building with yeast to elucidate an artificial pathway for de novo biosynthesis of glabridin.
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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7 authors.
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Abstract
Prenylated phytochemicals like glabridin are valuable therapeutics and cosmetics, yet their plant scarcity and arduous synthesis hinder industrial supply. Rebuilding pathways in microbes is hampered by complex topology and carbon-cofactor competition. In this work, we design an artificial biosynthetic route using a "block-building" workflow, constructing independently optimizable upstream precursor-supply and downstream tailoring/prenylation blocks. Structure-informed retrosynthesis eliminates methylation to lock flux toward the isoflavone core, while a tunable yeast-embedded dimethylallyl pyrophosphate platform enables crucial prenylation. Screening alternative pterocarpan reductase sources resolves the rate-limiting pentacyclic ring-opening step, achieving glabridin synthesis. Hybridization serves as the block glue, enabling the diploid Saccharomyces cerevisiae strain to produce 0.24 mg/L of glabridin from glucose, with bioreactor validation reaching 1.20 mg/L. Extending this to a yeast × Escherichia coli consortium delivers 32.8 mg/L equol, confirming framework generality. In this work, the strategy converts intricate phytochemical pathways into plug-and-play genetic modules, enabling rapid fermentation-based manufacturing without extensive genome rewriting.
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