Glyceollins are phytoalexins produced by soybeans in response to stressors such as pathogen invasion, injury, and environmental challenges. While these compounds exhibit diverse bioactivities, their limited accessibility hinders further physiological and biochemical studies. Additionally, the incomplete understanding of glyceollin biosynthesis, particularly the final cyclization steps, remains a major barrier to achieving sustainable production through synthetic biology. In this study, we elucidate the complete biosynthetic pathway of glyceollins through a combinatorial approach involving transient expression in Nicotiana benthamiana, in vitro enzyme characterization, and yeast feeding studies. We identified previously uncharacterized genes encoding reductases for 7,2',4'-trihydroxyisoflavanol (THI) biosynthesis and five P450 enzymes that mediate the final oxidative cyclization to produce glyceollins I, II, and III. By reconstructing the pathway de novo through synthetic biology and metabolic engineering, we achieved the successful production of glyceollins from simple carbon sources in baker's yeast. This work advances the understanding of glyceollin biosynthesis in soybean, facilitates sustainable production in microbial hosts and offers new opportunities for their application in agriculture and biology.

• PMID: 40211535
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Journal Article

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Sun Y, Chen C, Lin C, Zhang H, Lian J, Hong B

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