An integrated analysis of the rosmarinic acid-biosynthetic genes to uncover the regulation of rosmarinic acid pathway in Salvia miltiorrhiza

Song, Jie; Ji, Yanyun; Xu, Kun; Wang, Zhezhi

doi:10.1007/s11738-012-0948-4

Cited by 18 publications

(11 citation statements)

References 31 publications

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“…Among the 116 CYP450 genes, eight genes have been previously characterized. For example, one CYP450, SmCYP73A120, was previously identified as cinnamate 4-hydroxylase (C4H) and three CYP450s, SmCYP98A75, SmCYP98A76 and SmCYP98A77, were previously identified as β-coumaryl-CoA 3′-hydroxylase (CS3′H, ACA64046), β-coumaroyl shikimate 3′-hydroxylase (CS’3H, ACA64047) and β-coumarate 3-hydroxylase (C3H, ACA64048), respectively, which are directly linked to the accumulation of rosmarinic acid (RA) and its derivative, salvianolic acid B (SAB), in S. miltiorrhiza [39] . In addition, SmCYP98A78, which is the allelic variant of SmCYP98A14 (accession no.…”

Section: Discussionmentioning

confidence: 99%

Computational Identification and Systematic Classification of Novel Cytochrome P450 Genes in Salvia miltiorrhiza

Chen

Nelson

et al. 2014

PLoS ONE

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Salvia miltiorrhiza is one of the most economically important medicinal plants. Cytochrome P450 (CYP450) genes have been implicated in the biosynthesis of its active components. However, only a dozen full-length CYP450 genes have been described, and there is no systematic classification of CYP450 genes in S. miltiorrhiza. We obtained 77,549 unigenes from three tissue types of S. miltiorrhiza using RNA-Seq technology. Combining our data with previously identified CYP450 sequences and scanning with the CYP450 model from Pfam resulted in the identification of 116 full-length and 135 partial-length CYP450 genes. The 116 genes were classified into 9 clans and 38 families using standard criteria. The RNA-Seq results showed that 35 CYP450 genes were co-expressed with CYP76AH1, a marker gene for tanshinone biosynthesis, using r≥0.9 as a cutoff. The expression profiles for 16 of 19 randomly selected CYP450 obtained from RNA-Seq were validated by qRT-PCR. Comparing against the KEGG database, 10 CYP450 genes were found to be associated with diterpenoid biosynthesis. Considering all the evidence, 3 CYP450 genes were identified to be potentially involved in terpenoid biosynthesis. Moreover, we found that 15 CYP450 genes were possibly regulated by antisense transcripts (r≥0.9 or r≤–0.9). Lastly, a web resource (SMCYP450, http://www.herbalgenomics.org/samicyp450) was set up, which allows users to browse, search, retrieve and compare CYP450 genes and can serve as a centralized resource.

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Section: Discussionmentioning

confidence: 99%

Computational Identification and Systematic Classification of Novel Cytochrome P450 Genes in Salvia miltiorrhiza

Chen

Nelson

et al. 2014

PLoS ONE

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“…Methods to enhance the production of phenolic acids are mainly based on genetic engineering and elicitors. In genetic engineering methods, key enzyme genes in the phenolic acid biosynthesis pathway [e.g., PAL Wang 2009, 2011), 4CL,C4H, HPPR, HPPD , and RAS (Song et al 2012)] are overexpressed to induce accumulation of phenolic acids at different levels. Elicitors include various stresses: heavy metals [e.g., Ag (Xing et al 2015;Yan et al 2006) and Ce (Han et al 2015)], phytohormone [e.g., MeJA , ABA, PEG, and GA ], biotic elicitors [(e.g., yeast extract (Chen and Chen 2000), and fungus extract (Zhang et al 2014b)].…”

Section: Introductionmentioning

confidence: 99%

Phosphate starvation promoted the accumulation of phenolic acids by inducing the key enzyme genes in Salvia miltiorrhiza hairy roots

et al. 2016

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Phosphate starvation increased the production of phenolic acids by inducing the key enzyme genes in a positive feedback pathway in Saliva miltiorrhiza hairy roots. SPX may be involved in this process. Salvia miltiorrhiza is a wildly popular traditional Chinese medicine used for the treatment of coronary heart diseases and inflammation. Phosphate is an essential plant macronutrient that is often deficient, thereby limiting crop yield. In this study, we investigated the effects of phosphate concentration on the biomass and accumulation of phenolic acid in S. miltiorrhiza. Results show that 0.124 mM phosphate was favorable for plant growth. Moreover, 0.0124 mM phosphate was beneficial for the accumulation of phenolic acids, wherein the contents of danshensu, caffeic acid, rosmarinic acid, and salvianolic acid B were, respectively, 2.33-, 1.02-, 1.68-, and 2.17-fold higher than that of the control. By contrast, 12.4 mM phosphate inhibited the accumulation of phenolic acids. The key enzyme genes in the phenolic acid biosynthesis pathway were investigated to elucidate the mechanism of phosphate starvation-induced increase of phenolic acids. The results suggest that phosphate starvation induced the gene expression from the downstream pathway to the upstream pathway, i.e., a feedback phenomenon. In addition, phosphate starvation response gene SPX (SYG1, Pho81, and XPR1) was promoted by phosphate deficiency (0.0124 mM). We inferred that SPX responded to phosphate starvation, which then affected the expression of later responsive key enzyme genes in phenolic acid biosynthesis, resulting in the accumulation of phenolic acids. Our findings provide a resource-saving and environmental protection strategy to increase the yield of active substance in herbal preparations. The relationship between SPX and key enzyme genes and the role they play in phenolic acid biosynthesis during phosphate deficiency need further studies.

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Section: Transcription Factors In Salvianolic Acid Biosynthesismentioning

confidence: 99%

“…Song et al [62] comprehensively analysed and categorized the cis-acting regulatory elements in the biosynthetic genes of the RA pathway into five major groups according to their functions. The five major groups included typical consensus elements in eukaryotic promoters as well as ones responsive to light or stress, hormonal regulation and MYB-related roles [62]. On the basis of qRT-PCR analysis, co-expression analysis, and the prediction of cis-regulatory elements in the promoters, Ji et al [46] proposed that Sm008 and Sm166, which belong to the ERF-B1 and ERF-B4 subgroups, could regulate the biosynthesis of phenolic acid.…”

Section: Transcription Factors In Salvianolic Acid Biosynthesismentioning

confidence: 99%

Biosynthesis of bioactive ingredients of Salvia miltiorrhiza and advanced biotechnologies for their production

Geng²,

Zhao

2018

Biotechnology & Biotechnological Equipment

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This review deals with the progress in the biosynthesis and regulation of tanshinones and salvianolic acids as well as the prospects and challenges for producing such compounds through biotechnology techniques. Tanshinones (lipophilic diterpenoids) and salvianolic acids (hydrophilic phenolic acids) are valuable natural products from danshen (Salvia miltiorrhiza Bunge) with remarkable clinical efficacy to treat cardiovascular diseases, with potential application in the treatment of cancer and possibly other disorders. The significant bioactivities of S. miltiorrhiza inspired scientists to explore its biosynthetic mechanism that promotes the production of these compounds. Computational and comparative genomics and transcriptomics have been used to analyse a number of pathway genes, transcription factors and microRNAs that are associated with the biosynthesis and regulation of tanshinones and salvianolic acids. At the same time, plant cell and tissue culture, transgenic plants, microbial biotransformation and metabolic engineering have been used to synthesise all these compounds.

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An integrated analysis of the rosmarinic acid-biosynthetic genes to uncover the regulation of rosmarinic acid pathway in Salvia miltiorrhiza

Cited by 18 publications

References 31 publications

Computational Identification and Systematic Classification of Novel Cytochrome P450 Genes in Salvia miltiorrhiza

Computational Identification and Systematic Classification of Novel Cytochrome P450 Genes in Salvia miltiorrhiza

Phosphate starvation promoted the accumulation of phenolic acids by inducing the key enzyme genes in Salvia miltiorrhiza hairy roots

Biosynthesis of bioactive ingredients of Salvia miltiorrhiza and advanced biotechnologies for their production

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