Combining metabolomics and transcriptomics to characterize tanshinone biosynthesis in Salvia miltiorrhiza.
Combining metabolomics and transcriptomics to characterize tanshinone biosynthesis in Salvia miltiorrhiza.
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结合代谢组学和转录组学来表征丹参中丹参酮的生物合成
DOI：
10.1186/1471-2164-15-73
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发表时间：
2014-01-28
期刊：
影响因子：
4.4
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Gao W;Sun HX;Xiao H;Cui G;Hillwig ML;Jackson A;Wang X;Shen Y;Zhao N;Zhang L;Wang XJ;Peters RJ;Huang L
背景
几千年来，植物天然产品一直被人类用于各种用途，如调味品、香料和药物。这些化合物通常只能以相对较低的量生产，而且很难化学合成，从而限制了获取途径。虽然阐明潜在的生物合成过程可能有助于缓解这些问题(例如，通过代谢工程)，但相关基因的低水平表达和相应酶基因家族的扩大阻碍了对这一问题的研究。然而，这种代谢过程往往是可诱导的，这使得能够选择那些表达模式表明在目标天然产物的生产中发挥作用的基因。
结果
在这里，我们结合代谢组学和转录组学来研究从中草药丹参中诱导合成具有生物活性的丹参酮二萜类化合物。对诱导的毛状根培养物进行的非靶向代谢组学研究表明，丹参酮的产生是代谢反应的主要成分，并在随后的时间点增加。应用转录转录方法不仅定义了一个全面的转录组(由20,972个非冗余基因组成)，而且还定义了它对诱导的反应，揭示了6,358个基因表现出差异表达，并显著丰富了参与应激、刺激和免疫反应过程的基因的上调。与我们的代谢组学分析一致，二萜类化合物，更具体地说，丹参酮生物合成的已知基因的转录水平似乎有较慢但更持续的增加。共调控基因包括70个转录因子和8个细胞色素P450，为进一步研究提供了靶点。
结论
我们的结果表明，丹参萜类代谢对激发具有两相反应，早期诱导倍半萜和三萜类生物合成，随后较晚和更持久地产生二萜丹参酮。我们的数据为进一步阐明丹参酮和其他可诱导的天然产物在丹参的代谢提供了坚实的基础。
Background
Plant 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.
Results
Here, 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.
Conclusions
Our 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.
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