Combining metabolomics and transcriptomics to characterize tanshinone biosynthesis in Salvia miltiorrhiza

BMC Genomics

Research Article

Reuben J Peters¹  Alana Jackson¹  Matthew L Hillwig¹  Liangxiao Zhang²  Nan Zhao²  Hongbin Xiao²  Guanghong Cui³  Luqi Huang³  Ye Shen³  Xiao Wang³  Wei Gao⁴  Hai-Xi Sun⁵  Xiu-Jie Wang⁵ 

[1] Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, 50011, Ames, Iowa, USA;Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023, Dalian, China;National Resource Center for Chinese Materia Medica, Academy of Chinese Medical Sciences, 100700, Beijing, China;National Resource Center for Chinese Materia Medica, Academy of Chinese Medical Sciences, 100700, Beijing, China;School of Traditional Chinese Medicine, Capital Medical University, 100069, Beijing, China;State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China;

关键词: Hairy Root;    Differentially Express Gene;    Hairy Root Culture;    Tanshinone;    Reference Transcriptome;   

DOI  :  10.1186/1471-2164-15-73

 received in 2013-06-18, accepted in 2014-01-21,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundPlant natural products have been co-opted for millennia by humans for various uses such as flavor, fragrances, and medicines. These compounds often are only produced in relatively low amounts and are difficult to chemically synthesize, limiting access. While elucidation of the underlying biosynthetic processes might help alleviate these issues (e.g., via metabolic engineering), investigation of this is hindered by the low levels of relevant gene expression and expansion of the corresponding enzymatic gene families. However, the often-inducible nature of such metabolic processes enables selection of those genes whose expression pattern indicates a role in production of the targeted natural product.ResultsHere, we combine metabolomics and transcriptomics to investigate the inducible biosynthesis of the bioactive diterpenoid tanshinones from the Chinese medicinal herb, Salvia miltiorrhiza (Danshen). Untargeted metabolomics investigation of elicited hairy root cultures indicated that tanshinone production was a dominant component of the metabolic response, increasing at later time points. A transcriptomic approach was applied to not only define a comprehensive transcriptome (comprised of 20,972 non-redundant genes), but also its response to induction, revealing 6,358 genes that exhibited differential expression, with significant enrichment for up-regulation of genes involved in stress, stimulus and immune response processes. Consistent with our metabolomics analysis, there appears to be a slower but more sustained increased in transcript levels of known genes from diterpenoid and, more specifically, tanshinone biosynthesis. Among the co-regulated genes were 70 transcription factors and 8 cytochromes P450, providing targets for future investigation.ConclusionsOur results indicate a biphasic response of Danshen terpenoid metabolism to elicitation, with early induction of sesqui- and tri- terpenoid biosynthesis, followed by later and more sustained production of the diterpenoid tanshinones. Our data provides a firm foundation for further elucidation of tanshinone and other inducible natural product metabolism in Danshen.

【 授权许可】

Unknown   
© Gao et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.