丹参中丹参酮类物质的生物合成及其调控研究进展
Biosynthesis of Tanshinone and Its Regulation in Salvia miltiorrhiza*
DOI: 10.12677/BR.2013.23013, PDF, HTML, XML,  被引量 下载: 4,259  浏览: 18,607  国家自然科学基金支持
作者: 杨 蕾：国科学院上海辰山植物科学研究中心，上海辰山植物园，上海
关键词: 丹参；丹参酮；次生代谢；生物合成；调控； Salvia miltiorrhiza; Tanshinone; Secondary Metabolism; Biosynthesis; Regulation
摘要:

丹参(Salvia miltiorrhiza)为唇形科(Labiatae)鼠尾草属常用中药，以根和根茎入药，药理学表明丹参中丹参酮类化合物对于治疗心脑血管疾病具有显著疗效。据报道丹参酮作为丹参中的次生代谢产物，其生物合成途径受到各种生物及非生物因子的诱导调控。本文综述了近年来丹参酮类物质的生物合成，对其生物合成途径中关键酶基因及其诱导调控的相关研究进行了归纳总结，并对基因工程方法来提高药用植物中有效成分的含量做出了展望。

Abstract: Salvia miltiorrhiza, whose root and rhizome were often used as medicine, was classified in family of Labiatae. Many studies showed that tanshinone has significant effects in cuing cardiovascular disease. As the secondary metabolites, it was reported that the biosynthesis for tanshinone was regulated by various biotic or abiotic factors. In the present article, new findings about the biosynthesis of tanshinone were discussed, many key genes in the biosynthesis pathway as well as many related investigation were summed. Moreover, a vision of futurity was also given on how to increase the product of active component from plant by gene engineering.
文章引用：杨蕾. 丹参中丹参酮类物质的生物合成及其调控研究进展[J]. 植物学研究, 2013, 2(3): 73-78. http://dx.doi.org/10.12677/BR.2013.23013

参考文献

[1] 陈大为, 王宝玲. 神农本草经图鉴[J]. 天津: 天津科学技术出版社, 2009.
[2] S. A. V. Alvarenga, J. P. Gastmans AND G. V. Rodrigues. A com- puter-assisted approach for chemotaxonomic studies-diterpenes in Lamiaceae. Phytochemistry, 2001, 56(6): 583-595.
[3] L. Zhou, Z. Zuo AND M. S. S. Chow. Danshen: An overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. Journal of Clinical Pharmacology, 2005, 45(12): 1345-1359.
[4] X. Wang, S. L. Morris-Natschke and K. H. Lee. New develop- ments in the chemistry and biology of the bioactive constituents of Tanshen. Medicinal Research Reviews, 2007, 27(1): 133-148.
[5] K. K. Wong, T. W. Ho, H. Q. Lin, K. F. Lau, J. A. Rudd, C. K. Chung, K. P. Fung, P. C. Shaw and C. C. D. Wan. Crypto- tanshinone, an acetyl-cholinesterase inhibitor from Salvia milti- orrhiza, ameliorates scopolamine-induced amnesia in Morris water maze task. Planta Medica, 2010, 76(3): 228-234.
[6] X. Yao, X. Q. Wang, S. L. Ma and B. Y. Chen. Sodium tans- hinone IIA solfonate derived from Salvia miltiorrhiza Bunge up-regulate the expression of prolactin releasing peptide (PrRP) in the medulla oblongata in ovariectomized rats. Biochemical Pharmacology, 2006, 72: 582-587.
[7] D. H. Kim, S. Kim, S. J. Jeon, K. H. Son, S. Lee, B. H. Yoon, J. H. Cheong, K. H. Ko and J. H. Ryu. Tanshinone I enhances learning and memory, and ameliorates memory impairment in mice via the extracellular signal-regulated kinase signalling pathway. British Journal of Pharmacology, 2009, 158(4): 1131- 1142.
[8] G. Honda, Y. Koezuka and M. Tabata. Isolation of an antidermatophytic substance from the root of Salvia miltiorrhiza. Chemical & Pharmaceutical Bulletin, 1988, 36: 408-411.
[9] B. Nur Tana, M. Kalogaa and O. A. Radtke. Abietane diter- penoids and triterpenoic acids from Salvia cilicica and their antileishmanial activities. Phytochemistry, 2002, 61(8): 881-884.
[10] S. T. Withers and J. D. Keasling. Biosynthesis and engineering of isoprenoid small molecules. Applied Microbiology and Biotechnology, 2007, 73(5): 980-990.
[11] M. H. Hsieh and H. M. Goodman. The arabidopsis IspH homo- log is involved in the plastid nonmevalonate pathway of iso- prenoid biosynthesis. Plant Physiology, 2005, 138(2): 641-653.
[12] M. Seemann, B. Tse Sum Bui, M. Wolff, M. Miginiac-Maslow and M. Rohmer. Isoprenoid biosynthesis in plang chloroplasts via the Mep pathway: Direct thylakoid/ferredoxin-dependent photoreduction of GcpE/IspG. FEBS Letters, 2006, 580(6): 1547-1552.
[13] M. Köksal, Y. Jin, R. M. Coates, R. Croteau and D. W. Chris- tianson. Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis. Nature, 2011, 469(7328): 116-122.
[14] D. M. Martin, J. Faldt and J. Bohlmann. Functional charac- terization of nine Norway Spruce TPS genes and evolution of gymnosperm terpene synthases of the TPS-d subfamily. Plant Physiology, 2004, 135(4): 1908-1927.
[15] S. J. Wu, M. Shi and J. Y. Wu. Cloning and characterization of the I-deoxy-D-xylulose 5-phosphate reductoisomerase gene for diterpenoidtanshinone biosynthesis in Salvia miltiorrhiza (Chin- ses sage) hairy roots. Biotechnology and Applied Biochemistry, 2009, 52(1): 89-95.
[16] J. W. Wang and J. Y. Wu. Tanshinone biosynthesis in Salvia miltiorrhiza and production in plant tissue cultures. Applied Microbiology and Biotechnology, 2010, 88(2): 437-449.
[17] Z. Dai, G. Cui, S. F. Zhou, X. Zhang and L. Huang. Cloning and characterization of a novel 3-hydroxy-3-methylglutaryl coen- zyme A reductase gene from Salvia miltiorrhiza involved in diterpenoidtanshinone accumulation. Journal of Plant Phy- siology, 2011, 168(2): 148-157.
[18] G. Kai, H. Xu, C. Zhou, P. Liao, J. Xiao, X. Luo, L. You and L. Zhang. Metabolic engineering tanshinone biosynthetic pathway in Salvia miltiorrhiza. Metabolic Engineering, 2011, 13(3): 319- 327.
[19] D. Ma, G. Pu, C. Lei, L. Ma, H. Wang, Y. Guo, J. Chen, Z. Du, G. Li, H. Ye and B. Liu. Isolation and characterization of AaWRKY1, an Artemisia annua transcription factor that regu- lates the amorpha-4,11-diene synthase gene, a key gene of arte- misin in biosynthesis. Plant and Cell Physiology, 2009, 50(12): 2146-2161.
[20] W. Gao, M. L. Hillwig, L. Q. Huang, G. H. Cui, X. Y. Wang, J. Q. Kong, B. Yang and R. J. Peters. Functional genomics approach to tanshinone biosynthesis provides stereochemical in sighs. Organic Letters, 2009, 11(22): 5170-5173.
[21] M. L. Hillwig, M. Xu, T. Toyomasu, M. S. Tiernan, G. Wei, G. Cui, L. Huang and R. J. Peters. Domain loss has independently occurred multiple times in plant terpene synthase evolution. Plant Journal, 2011, 68(6): 1051-1060.
[22] J. Guo, Y. J. Zhou, M. L. Hillwig, Y. Shen, L. Yang, Y. J. Wang, X. A. Zhang, W. J. Liu, R. J. Peters, X. Y. Chen, Z. K. Zhao and L. Q. Huang. CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts. PNAS, 2013, in press.
[23] M. L. Metzker. Sequencing technologies-the next generation. Nature Genetics, 2010, 11(1): 31-46.
[24] W. Hua, Y. Zhang, J. Song, L. Zhao and Z. Wang. De novo transcriptome sequencing in Salvia miltiorrhiza to identify genes involved in the biosynthesis of active ingredients. Genomics, 2011, 98(4): 272-279.
[25] 倪学斌, 苏静. 丹参地上部分有效成分的初步分析[j]. 中国药学杂志, 1995, 30(6): 336-338.
[26] J. Gershenzon. Changes in the levels of plant secondary meta- bolites under water and nutrient stress. New York: Plenum Press, 1984: 273-320.
[27] A. L. Shelton. Variable chemical defences in plants and their effects on herbivore behavior. Evolutionary Ecology Research, 2000, 2(2): 231-249.
[28] 陈晓亚, 刘培. 植物次生代谢的分子生物学及基因工程[J]. 生命科学, 1996, 8(2): 8-11.
[29] L. Zhang, X. Yan, J. Wang, S. Li, P. Liao and G. Kai. Molecular cloning and expression analysis of a new putative gene encoding 3-hydroxy-3-methylglutaryl-CoA synthase from Salvia milti- orrhiza. Acta Physiologiae Plantarum, 2011, 33(3): 953-961.
[30] H. Chen and F. Chen. Effects of yeast elicitor on the growth and secondary metabolism of a high-tanshinone-producing line of the Ti transformed Salvia miltiorrhiza cells in suspension culture. Process Biochemistry, 2000, 35(8): 837-840.
[31] J L Zhao, L G Zhou and J Y Wu. Effects of biotic and abiotic elicitors on cell growth and tanshinone accumulation in Salvia miltiorrhiza cell cultures. Applied Microbiology and Biotech- nology, 2010, 87(1): 137-144.
[32] X. C. Ge and J. Y. Wu. Tanshinone production and isoprenoid pathways in Salvia miltiorrhiza hairy roots induced by Ag+ and yeast elicitor. Plant Science, 2005, 168(2): 487-491.
[33] M. Shi, K. W. Kwok and J. Y. Wu. Enhancement of tanshinone production in Salvia miltiorrhiza Bunge (red or Chinese sage) hairy-root culture by hyperosmotic stress and yeast elicitor. Bio- technology and Applied Biochemistry, 2007, 46(Pt 4): 191-196.
[34] N. De Geyter, A. Gholami, S. Goormachtig and A. Goossens. Transcriptional machineries in jasmonate-elicited plant second- dary metabolism. Trends in Plant Science, 2012, 17(6): 349-359.
[35] C. Q. Yang, X. Fang, X. M. Wu, Y. B. Mao, L. J. Wang and X. Y. Chen. Transcriptional regulation of plant secondary metabolism. Journal of Integrative Plant Biology, 2012, 54(10): 703-712.
[36] M. Skibbe, N. Qu, I. Galis and I. T. Baldwin. Induced plant de- fenses in the natural environment: Nicotiana attenuata WRKY3 and WRKY6 coordinate responses to herbivory. Plant Cell, 2008, 20(7): 1984-2000.
[37] Y. H. Xu, J. W. Wang, S. Wang, J. Y. Wang and X. Y. Chen. Characterization of GaWRKY1, a cotton transcription factor that regulates these squiterpene synthase gene (+)-delta-cadinene synthase-A. Plant Physiology, 2004, 135(1): 507-515.
[38] Z. X. Yu, J. X. Li, C. Q. Yang, W. L. Hu, L. J. Wang and X. Y. Chen. The jasmonate-responsive AP2/ERF transcription factors AaERF1 and AaERF2 positively regulate artemisinin biosyn- thesis in Artemisia annua L. Molecular Plant, 2012, 5(2): 353- 365.
[39] G. J. Hong, X. Y. Xue, Y. B. Mao, L. J. Wang and X. Y. Chen. Arabidopsis MYC2 interacts with DELLA proteins in regulating sesquiterpene synthase gene expression. Plant Cell Online, 2012, 24(6): 2635-2648.