title: Gene-to-metabolite network for biosynthesis of lignans in MeJA-elicited Isatis indigotica hairy root cultures.
abstract: Root and leaf tissue of Isatis indigotica shows notable anti-viral efficacy, and are widely used as "Banlangen" and "Daqingye" in traditional Chinese medicine. The plants' pharmacological activity is attributed to phenylpropanoids, especially a group of lignan metabolites. However, the biosynthesis of lignans in I. indigotica remains opaque. This study describes the discovery and analysis of biosynthetic genes and AP2/ERF-type transcription factors involved in lignan biosynthesis in I. indigotica. MeJA treatment revealed differential expression of three genes involved in phenylpropanoid backbone biosynthesis (IiPAL, IiC4H, Ii4CL), five genes involved in lignan biosynthesis (IiCAD, IiC3H, IiCCR, IiDIR, and IiPLR), and 112 putative AP2/ERF transcription factors. In addition, four intermediates of lariciresinol biosynthesis were found to be induced. Based on these results, a canonical correlation analysis using Pearson's correlation coefficient was performed to construct gene-to-metabolite networks and identify putative key genes and rate-limiting reactions in lignan biosynthesis. Over-expression of IiC3H, identified as a key pathway gene, was used for metabolic engineering of I. indigotica hairy roots, and resulted in an increase in lariciresinol production. These findings illustrate the utility of canonical correlation analysis for the discovery and metabolic engineering of key metabolic genes in plants.
authors.affiliation: Department of Pharmaceutical Botany, School of Pharmacy, Second Military Medical University Shanghai, China.
authors.forename: Ruibing
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Shanghai Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Botany, School of Pharmacy, Second Military Medical University Shanghai, China.
authors.forename: Hexin
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Pharmacy, Shanghai Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Shanghai Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University Shenyang, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, Shanghai Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Shouhong
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Plant Biology, University of California, Davis Davis, CA, USA.
authors.forename: Philipp
authors.initials: P
authors.lastname: Zerbe
authors.affiliation: Department of Pharmacy, Shanghai Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Wansheng
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Botany, School of Pharmacy, Second Military Medical University Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
keywords: AP2/ERF; Isatis indigotica; biosynthesis of lignans; gene-metabolic network; metabolic engineering