title: Inducing effect of dihydroartemisinic acid in the biosynthesis of artemisinins with cultured cells of Artemisia annua by enhancing the expression of genes.
abstract: Artemisinin has been used in the production of "artemisinin combination therapies" for the treatment of malaria. Feeding of precursors has been proven to be one of the most effective methods to enhance artemisinin production in plant cultured cells. At the current paper, the biosynthesis of artemisinin (ART) and its four analogs from dihydroartemisinic acid (DHAA) in suspension-cultured cells of Artemisia annua were investigated. ARTs were detected by HPLC/GC-MS and isolated by various chromatography methods. The structures of four DHAA metabolites, namely, dihydro-epi-deoxyarteannuin B, arteannuin I, arteannuin K, and 3-β-hydroxy-dihydro-epi-deoxyarteannuin B, were elucidated by physicochemical and spectroscopic analyses. The correlation between gene expression and ART content was investigated. The results of RT-PCR showed that DHAA could up-regulate expression of amorpha-4,11-diene synthase gene (ADS), amorpha-4,11-diene C-12 oxidase gene (CYP71AV1), and farnesyl diphosphate synthase gene (FPS) (3.19-, 7.21-, and 2.04-fold higher than those of control group, resp.), which indicated that biosynthesis processes from DHAA to ART were enzyme-mediated.
authors.affiliation: Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou 510632, China.
authors.forename: Jianhua
authors.identifier: 0000-0002-9706-1437
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou 510632, China.
authors.forename: Jiazeng
authors.initials: J
authors.lastname: Yang
authors.affiliation: Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou 510632, China.
authors.forename: Zihan
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou 510632, China.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou 510632, China ; College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Song
authors.affiliation: Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou 510632, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
authors.affiliation: Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou 510632, China ; College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Rongmin
authors.initials: R
authors.lastname: Yu
mesh_terms: D031172:Artemisia annua / Q000187:drug effects* / Q000378:metabolism*; D037621:Artemisinins / Q000378:metabolism* / Q000494:pharmacology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D018506:Gene Expression Regulation, Plant / Q000187:drug effects; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D037621:Artemisinins; D010940:Plant Proteins; C520462:dihydroartemisinic acid; C031327:artemisinin