2. Academic Validation
  3. Elucidation and de novo reconstitution of glyceollin biosynthesis

Elucidation and de novo reconstitution of glyceollin biosynthesis

  • Mol Plant. 2025 May 5;18(5):820-832. doi: 10.1016/j.molp.2025.04.003.
Yunlong Sun 1,  Cong Chen 2,  Chao Lin 1,  Hao Zhang 1,  Jiazhang Lian 3,  Benke Hong 4
Affiliations

Affiliations

  • 1 Zhejiang Key Laboratory of Precise Synthesis of Functional Molecules, Department of Chemistry, School of Science and Research Center for Industries of the Future, Westlake University, Hangzhou, China.
  • 2 Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.
  • 3 Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China; Zhejiang Key Laboratory of Intelligent Manufacturing for Functional Chemicals, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, China. Electronic address: jzlian@zju.edu.cn.
  • 4 Zhejiang Key Laboratory of Precise Synthesis of Functional Molecules, Department of Chemistry, School of Science and Research Center for Industries of the Future, Westlake University, Hangzhou, China. Electronic address: hongbenke@westlake.edu.cn.
PMID: 40211535 DOI: 10.1016/j.molp.2025.04.003
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.

Keywords

Glycine max; biosynthetic pathway; glyceollins; phytoalexins; soybean; synthetic biology.

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