{"title":"Elucidation and de novo reconstitution of glyceollin biosynthesis.","authors":"Yunlong Sun, Cong Chen, Chao Lin, Hao Zhang, Jiazhang Lian, Benke Hong","doi":"10.1016/j.molp.2025.04.003","DOIUrl":null,"url":null,"abstract":"<p><p>Glyceollins are phytoalexins, soybean-produced compounds that respond to pathogen invasion, injury, and environmental challenges. While these compounds have diverse bioactivities, their limited accessibility hinders further physiological and biochemical studies. Additionally, the incomplete understanding of glyceollin biosynthesis, particularly cyclization steps, remains a major barrier to sustainable production through synthetic biology. In this study, we uncover 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 biosynthesis and five P450 enzymes that mediate the final oxidative cyclization to produce glyceollins I, II, and III. By de novo reconstruction of the pathway through synthetic biology and metabolic engineering, we successfully produced glyceollins from simple carbon sources in baker's yeast. This work advances the understanding of glyceollin biosynthesis in soybeans, enables sustainable production in microbial hosts, and offers new opportunities for their application in agriculture and biology.</p>","PeriodicalId":19012,"journal":{"name":"Molecular Plant","volume":"18 5","pages":"820-832"},"PeriodicalIF":17.1000,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Plant","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.molp.2025.04.003","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/10 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Glyceollins are phytoalexins, soybean-produced compounds that respond to pathogen invasion, injury, and environmental challenges. While these compounds have diverse bioactivities, their limited accessibility hinders further physiological and biochemical studies. Additionally, the incomplete understanding of glyceollin biosynthesis, particularly cyclization steps, remains a major barrier to sustainable production through synthetic biology. In this study, we uncover 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 biosynthesis and five P450 enzymes that mediate the final oxidative cyclization to produce glyceollins I, II, and III. By de novo reconstruction of the pathway through synthetic biology and metabolic engineering, we successfully produced glyceollins from simple carbon sources in baker's yeast. This work advances the understanding of glyceollin biosynthesis in soybeans, enables sustainable production in microbial hosts, and offers new opportunities for their application in agriculture and biology.
期刊介绍:
Molecular Plant is dedicated to serving the plant science community by publishing novel and exciting findings with high significance in plant biology. The journal focuses broadly on cellular biology, physiology, biochemistry, molecular biology, genetics, development, plant-microbe interaction, genomics, bioinformatics, and molecular evolution.
Molecular Plant publishes original research articles, reviews, Correspondence, and Spotlights on the most important developments in plant biology.