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

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Abstract

Medicinal Salvia miltiorrhiza is renowned for its curative effects on cardiovascular diseases. Its biologically active ingredients include rosmarinic acid (RA) and its derivative, salvianolic acid B (SAB). We used available bioinformatics tools to improve our knowledge about the biosynthesis of these phenolic compounds. Our comprehensive description of cis-acting regulatory elements in the RA pathway provides insights into the potential transcriptional regulation of that pathway. For example, a light-responsive element was the most abundant and widespread motif, suggesting that light is a universal regulatory factor of RA synthesis in S. miltiorrhiza. Therefore, we examined gene transcripts and the accumulation of hydrophilic pharmacological compounds in light-treated plants. Canonical correlation analysis was also used to construct a gene-to-metabolite network. We obtained a high correlation coefficient (0.986), which generally indicated a clear and close relationship between RA-biosynthetic genes and desirable metabolites. We also screened PAL1, C4H, and HPPR, genes directly linked to the accumulation of RA and SAB. Our results can serve as the basis for better understanding RA synthesis in S. miltiorrhiza, and they will increase the practical potential for metabolic engineering of this important medicinal species.

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Acknowledgments

This work was supported by the 11th “five-year technique project” of the Ministry of Science and Technology of the People’s Republic of China (2006BAI06A12-04), and by the Postdoctoral Foundation of China (20110491648).

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Correspondence to Zhezhi Wang.

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Communicated by M. Stobiecki.

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Supporting Information: Additional Supporting Information may be found in the online version of this article:

Appendix S1 Nucleotide sequence of the 5′ flanking region of 4CL1 (TIFF 86 kb)

Appendix S2. Nucleotide sequence of the 5′ flanking region of 4CL2 (TIFF 124 kb)

Appendix S3. Nucleotide sequence of the 5′ flanking region of HPPR (TIFF 78 kb)

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Song, J., Ji, Y., Xu, K. et al. An integrated analysis of the rosmarinic acid-biosynthetic genes to uncover the regulation of rosmarinic acid pathway in Salvia miltiorrhiza . Acta Physiol Plant 34, 1501–1511 (2012). https://doi.org/10.1007/s11738-012-0948-4

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