Identification of a central regulator of ginkgolide biosynthesis in Ginkgo biloba that integrates jasmonate and light signaling

• 成果类型: Article
• 署名作者: Du, Jinfa; Zhao, Zhen; Jin, Lingqi; Huang, Lijin; Jin, Dian; Zheng, Xiaoyan; Wang, Qiaolei; Xu, Wenbo; Guo, Huijun; Xing, Xinyue; Alolga, Raphael N.; Tran, Lam-Son Phan; Herrera-Estrella, Luis Rafael; Li, Ping; Yin, Xiaojian; Lu, Xu
• 署名单位: China Pharmaceutical University; Chinese Academy of Sciences; Northeast Institute of Geography & Agroecology, CAS; Texas Tech University System; Texas Tech University; Instituto Politecnico Nacional - Mexico; CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional; China Academy of Chinese Medical Sciences; National Resource Center for Chinese Materia Medica, CACMS; China Pharmaceutical University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9237
• DOI: 10.1073/pnas.240889112
• 发表日期: 2025-02-11
• 关键词: artemisinin biosynthesis; transcription factors; living fossil; hy5; accumulation; FAMILY; leaves; TREE

摘要

Ginkgolides are secondary metabolites unique to Ginkgo biloba with the potential to prevent and treat cardiovascular and cerebrovascular diseases. Although the biosynthetic pathways of ginkgolides have been partly uncovered, the mechanism regulating their bio-synthesis is still largely unknown. Here, using multiomic and genetic analyses, we report the identification of a transcription factor, named ETHYLENE RESPONSE FACTOR ASSOCIATED WITH GINKGOLIDE BIOSYNTHESIS (GbEAG), as a critical regula-tor of ginkgolide biosynthesis. GbEAG is highly expressed in the roots of G. biloba, and its expression is significantly induced by methyl jasmonate (MeJA). Ginkgolide content was significantly increased in roots by overexpressing GbEAG using a cut- dip- regeneration system. GbEAG positively regulates ginkgolide biosynthesis by directly binding to the GCC- boxes in the promoter regions of genes involved in the biosynthesis of ginkgolides, such as ISOPENTENYL DIPHOSPHATE ISOMERASE (GbIDI) and CYTOCHROME P450 7005C3 (GbCYP7005C3). GbEAG mediates the jasmonic acid (JA)- activated gink-golide synthesis through its direct interaction with the JASMONATE ZINC- FINGER INFLORESCENCE MERISTEM DOMAIN 3 (GbJAZ3) repressor. Importantly, we also found that the central light- response regulator ELONGATED HYPOCOTYL 5 (GbHY5) mediates light induction of ginkgolide biosynthesis by binding to the G- box in the GbEAG promoter. Our findings provide mechanistic insights into the coordinated regulation of ginkgolide biosynthesis via JA and light signals, with GbEAG as a central regulator in G. biloba, and shed light on the potential to develop ginkgolide- rich varieties through molecular breeding and gene editing.