Tanshinone and salvianolic acid biosynthesis are regulated by SmMYB98 in Salvia miltiorrhiza hairy roots

Hao, Xiaolong; Pu, Zhongqiang; Cao, Gang; You, Dawei; Zhou, Yang; Deng, Changping; Shi, Min; Nile, Shivraj Hariram; Wang, Yao; Zhou, Wei; Kai, Guoyin

doi:10.1016/j.jare.2020.01.012

Cited by 118 publications

(90 citation statements)

References 46 publications

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“…Overexpressing SmMYB36 decreases salvianolic acid contents in S. miltiorrhiza hairy roots by inhibiting the expression of 4CL2, C4H1, and HPPR (Ding et al 2017). SmMYB98 increases salvianolic acid production by activating the expression of PAL1 and RAS1 (Hao et al 2020). In the present study, we demonstrated that SmMYB2 binds to the MBS1/MBS2/MRE elements in the CYP98A14 promoter, thereby activating its expression and promoting salvianolic acid accumulation.…”

Section: Smmyb2 Promotes Salvianolic Acid Biosynthesissupporting

confidence: 55%

“…MYB proteins comprise a huge family of TFs that play important roles in plant development and secondary metabolism (Borevitz et al 2000;Czemmel et al 2012;Chen et al 2019;Hao et al 2020). MYB TFs are classified into four subfamilies based on the number of conserved MYB domains in their N-terminal regions, 1R-MYB, R2R3-MYB, R1R2R3-MYB, and 4R-MYB TFs, with R2R3-MYBs representing the major subfamily in plants (Rosinski and Atchley 1998;Dubos et al 2010;An et al 2015;Wang et al 2019aWang et al , 2019bHao et al 2020). For example, NtMYB3 represses flavonol biosynthesis in Narcissus tazetta (Anwar et al 2019).…”

Section: Introductionmentioning

confidence: 99%

“…The R2R3-MYB TF MYB6 promotes anthocyanin and proanthocyanidin biosynthesis in Populus tomentosa (Wang et al 2019a(Wang et al , 2019b. Overexpressing R2R3-MYB TF SmMYB9b (Zhang et al 2017) or SmMYB98 (Hao et al 2020) enhanced tanshinone concentrations in S. miltiorrhiza.…”

Section: Introductionmentioning

confidence: 99%

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SmMYB2 promotes salvianolic acid biosynthesis in the medicinal herb Salvia miltiorrhiza

Deng

Wang

Huang

et al. 2020

JIPB

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MYB transcription factors play vital roles in plant growth and metabolism. The phytohormone methyl jasmonate (MeJA) promotes phenolic acid accumulation in the medicinal herb Salvia miltiorrhiza, but the regulatory mechanism is poorly understood. Here, we identified the MeJA-responsive R2R3-MYB transcription factor gene SmMYB2 from a transcriptome library produced from MeJAtreated S. miltiorrhiza hairy roots. SmMYB2 expression was tightly correlated with the expression of key salvianolic acid biosynthetic genes including CYP98A14. SmMYB2 was highly expressed in the periderm of S. miltiorrhiza and SmMYB2 localized to the nucleus. Overexpressing SmMYB2 in S. miltiorrhiza hairy roots significantly increased the levels of salvianolic acids (including rosmarinic acid and salvianolic acid B) by upregulating salvianolic acid biosynthetic genes such as CYP98A14. SmMYB2 binds to the MYB-binding motifs in the promoter of CYP98A14, as confirmed by a dual-luciferase assay and electrophoretic mobility shift assays. Anthocyanin contents were significantly higher in SmMYB2-overexpressing hairy root lines than the control, primarily due to the increased expression of CHI, DFR, and ANS. These findings reveal the novel regulatory role of SmMYB2 in MeJA-mediated phenolic acid biosynthesis, providing a useful target gene for metabolic engineering and shedding light on the salvianolic acid regulatory network.

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Section: Smmyb2 Promotes Salvianolic Acid Biosynthesissupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

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SmMYB2 promotes salvianolic acid biosynthesis in the medicinal herb Salvia miltiorrhiza

Deng

Wang

Huang

et al. 2020

JIPB

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“…Different O. pumila hairy-root lines were inoculated and cultured in liquid B5 medium at 120 rpm in darkness at 25 °C. Nicotiana benthamiana plants used for subcellular localization analyses of OpWRKY2 protein and dual-luciferase (Dual-LUC) assays to detect the activation of OpWRKY2 were grown in pots containing soil mixture and placed in a growth chamber under a light/dark photoperiod of 16/8 h at 25 °C 23 .…”

Section: Methodsmentioning

confidence: 99%

The transcription factor OpWRKY2 positively regulates the biosynthesis of the anticancer drug camptothecin in Ophiorrhiza pumila

et al. 2021

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The limited bioavailability of plant-derived natural products with anticancer activity poses major challenges to the pharmaceutical industry. An example of this is camptothecin, a monoterpene indole alkaloid with potent anticancer activity that is extracted at very low concentrations from woody plants. Recently, camptothecin biosynthesis has been shown to become biotechnologically amenable in hairy-root systems of the natural producer Ophiorrhiza pumila. Here, time-course expression and metabolite analyses were performed to identify novel transcriptional regulators of camptothecin biosynthesis in O. pumila. It is shown here that camptothecin production increased over cultivation time and that the expression pattern of the WRKY transcription factor encoding gene OpWRKY2 is closely correlated with camptothecin accumulation. Overexpression of OpWRKY2 led to a more than three-fold increase in camptothecin levels. Accordingly, silencing of OpWRKY2 correlated with decreased camptothecin levels in the plant. Further detailed molecular characterization by electrophoretic mobility shift, yeast one-hybrid and dual-luciferase assays showed that OpWRKY2 directly binds and activates the central camptothecin pathway gene OpTDC. Taken together, the results of this study demonstrate that OpWRKY2 acts as a direct positive regulator of camptothecin biosynthesis. As such, a feasible strategy for the over-accumulation of camptothecin in a biotechnologically amenable system is presented.

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“…The metabolic engineering of key TFs provides a feasible strategy for improving the content of tanshinones and other bioactive compounds ( Sun et al., 2019 ; Deng et al., 2020b ; Hao et al., 2020 ). As MYC2 orthologs are master regulators of JA-mediated secondary metabolite biosynthesis, metabolic engineering using Sm MYC2b as candidate can be a promising strategy to achieve high yield of target compounds in S. miltiorrhiza .…”

Section: Discussionmentioning

confidence: 99%

SmMYC2b Enhances Tanshinone Accumulation in Salvia miltiorrhiza by Activating Pathway Genes and Promoting Lateral Root Development

Zhou

Feng

et al. 2020

Front. Plant Sci.

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Salvia miltiorrhiza Bunge (Lamiaceae) is an economically important medicinal plant as well as an emerging model plant. Our previous studies indicate that SmMYC2b is a positive transcription factor that can affect the biosynthesis of phenolic acids and tanshinones in S. miltiorrhiza. Moreover, MYC2s are well known to induce the development of lateral roots. As tanshinones are mainly distributed in the periderm, the promotion of lateral root development probably leads to increased accumulation of tanshinones. In this paper, we firstly discovered that SmMYC2b played a dual regulatory role in effectively enhancing the tanshinone accumulation by activating tanshinone biosynthetic pathway and promoting lateral root development. The expression levels of the previously studied pathway genes SmCPS1, SmKSL1, SmCYP76AH1, SmCYP76AH3, and SmCYP76AK1 dramatically increased. In addition, SmMYC2b was proved to exhibit a similar function as other homologs in promoting lateral root development, which increased the tanshinone produced tissue and further enhanced the biosynthesis of tanshinones. RNA-seq assays revealed that SmMYC2b-regulated genes comprised 30.6% (1,901 of 6,210) of JA-responsive genes, confirming that SmMYC2b played a crucial role in transcriptional regulation of JA-regulated genes. Overall, we concluded that SmMYC2b could enhance tanshinone accumulation by activating the tanshinone biosynthetic pathway and promoting lateral root development. Our study provides an effective approach to enhance the production of desired tanshinones and enriches our knowledge of the related regulatory network.

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Tanshinone and salvianolic acid biosynthesis are regulated by SmMYB98 in Salvia miltiorrhiza hairy roots

Cited by 118 publications

References 46 publications

SmMYB2 promotes salvianolic acid biosynthesis in the medicinal herb Salvia miltiorrhiza

SmMYB2 promotes salvianolic acid biosynthesis in the medicinal herb Salvia miltiorrhiza

The transcription factor OpWRKY2 positively regulates the biosynthesis of the anticancer drug camptothecin in Ophiorrhiza pumila

SmMYC2b Enhances Tanshinone Accumulation in Salvia miltiorrhiza by Activating Pathway Genes and Promoting Lateral Root Development

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