Identification of a central regulator of ginkgolide biosynthesis in <i>Ginkgo biloba</i> that integrates jasmonate and light signaling
Abstract
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 biosynthesis 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 regulator 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 ginkgolide 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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (16)
Jinfa Du
Department of Pharmacognosy, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Zhen Zhao
Institute of Catalysis for Energy and Environment
Lingqi Jin
Department of Pharmacognosy, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Lijin Huang
Department of Pharmacognosy, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Dian Jin
Department of Pharmacognosy, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Xiaoyan Zheng
Qiaolei Wang
Department of Pharmacognosy, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Wenbo Xu
Department of Pharmacognosy, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Huijun Guo
Department of Pharmacognosy, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Xinyue Xing
Department of Pharmacognosy, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Raphael N. Alolga
Department of Pharmacognosy, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Lam-Son Phan Tran
Department of Plant and Soil Science, Institute of Genomics for Crop Abiotic Stress Tolerance, Texas Tech University
Luis Rafael Herrera-Estrella
State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, Zhongshan Biological Breeding Laboratory, Department of Plant Nutrition, College of Resources and Environmental Sciences, Nanjing Agricultural University
Ping Li
Xiaojian Yin
Department of Pharmacognosy, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Xu Lu
Department of Pharmacognosy, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University