title: A basic leucine zipper transcription factor, AabZIP1, connects abscisic acid signaling with artemisinin biosynthesis in Artemisia annua.
abstract: Artemisinin is a sesquiterpenoid especially synthesized in the Chinese herbal plant, Artemisia annua, which is widely used in the treatment of malaria. Artemisinin accumulation can be enhanced by exogenous abscisic acid (ABA) treatment. However, it is not known how ABA signaling regulates artemisinin biosynthesis. A global expression profile and phylogenetic analysis as well as the dual-LUC screening revealed that a basic leucine zipper family transcription factor from A. annua (namely AabZIP1) was involved in ABA signaling to regulate artemisinin biosynthesis. AabZIP1 had a higher expression level in the inflorescences than in other tissues; ABA treatment, drought, and salt stress strongly induced the expression of AabZIP1. Yeast one-hybrid assay and electrophoretic mobility shift assay (EMSA) showed that AabZIP1 bound to the ABA-responsive elements (ABRE) in the promoter regions of the amorpha-4,11-diene synthase (ADS) gene and CYP71AV1, which are two key structural genes of the artemisinin biosynthetic pathway. A mutagenesis assay showed that the C1 domain in the N-terminus of AabZIP1 was important for its transactivation activity. Furthermore, the activation of ADS and CYP71AV1 promoters by AabZIP1 was enhanced by ABA treatment in transient dual-LUC analysis. The AabZIP1 variant with C1 domain deletion lost the ability to activate ADS and CYP71AV1 promoters regardless of ABA treatment. Notably, overexpression of AabZIP1 in A. annua resulted in significantly increased accumulation of artemisinin. Our results indicate that ABA promotes artemisinin biosynthesis, likely through 1 activation of ADS and CYP71AV1 expression by AabZIP in A. annua. Meanwhile, our findings reveal the potential value of AabZIP1 in genetic engineering of artemisinin production.
authors.affiliation: Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Fu
authors.affiliation: Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Zongyou
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Lu
authors.affiliation: Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Sun
authors.affiliation: SWU-TAAHC Medicinal Plant Joint R&D Centre, School of Life Sciences, Southwest University, Chongqing 400715, China. Electronic address: zhliao@swu.edu.cn.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: kxtang@sjtu.edu.cn.
authors.forename: Kexuan
authors.initials: K
authors.lastname: Tang
mesh_terms: D000040:Abscisic Acid / Q000378:metabolism*; D031172:Artemisia annua / Q000378:metabolism*; D037621:Artemisinins / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D037621:Artemisinins; D050976:Basic-Leucine Zipper Transcription Factors; D014157:Transcription Factors; D000040:Abscisic Acid; C031327:artemisinin
keywords: Artemisia annua; abscisic acid (ABA); artemisinin; bZIP transcription factor; sesquiterpene