药学学报, 2020, 55(12): 2892-2903
引用本文:
詹忠根. 基于多组学的丹参活性成分生物合成与调控研究进展[J]. 药学学报, 2020, 55(12): 2892-2903.
ZHAN Zhong-gen. Advances in biosynthesis and regulation of the active ingredient of Salvia miltiorrhiza based on multi-omics approach[J]. Acta Pharmaceutica Sinica, 2020, 55(12): 2892-2903.

基于多组学的丹参活性成分生物合成与调控研究进展
詹忠根
浙江经贸职业技术学院生物制药教研室, 浙江 杭州 310018
摘要:
中药丹参(Salvia miltiorrhiza Bge.)具有很高的药用价值,对心血管疾病、肝硬化、慢性肾功能衰竭、阿尔茨海默病、心绞痛、心肌缺血、肝病、糖尿病、肾病具有治疗作用。近年来,随着丹参基原植物野生资源的短缺和栽培种质质量不稳定等问题的突显,其主要活性成分生物合成与调控机制研究成为国际关注的热点。而多组学技术在丹参研究中的应用和发展,为分子层面揭示丹参遗传信息及活性成分合成与调控机制研究提供了可能。本文在系统总结丹参基因组、转录组、蛋白质组和代谢组研究进展的基础上,归纳了丹参活性成分生物合成、调控及相关功能基因的研究概况,并提出未来亟待深入研究的科学问题,旨在为进一步发挥丹参在药用植物研究方面的模式作用提供参考。
关键词:    丹参      活性成分      生物合成与调控      多组学技术     
Advances in biosynthesis and regulation of the active ingredient of Salvia miltiorrhiza based on multi-omics approach
ZHAN Zhong-gen
Biopharmaceutical Laboratory, Zhejiang Institute of Economics and Trade, Hangzhou 310018, China
Abstract:
Salvia miltiorrhiza Bge. is one of the most important traditional Chinese medicinal plants and is used for a variety of diseases and disorders, including cardiovascular diseases, hepatocirrhosis, chronic renal failure, Alzheimer's disease, angina pectoris, myocardial ischemia, liver diseases, and diabetic nephropathy. In recent years, with the shortage of uncultivated resources and uneven product quality of cultivated germplasm, the biosynthesis and regulation of its main active ingredient has become a topic of interest. The use of a multi-omics approach with Salvia miltiorrhiza may provide genetic information as well as insights into the synthesis and regulation of the active ingredient at the molecular level. The paper presented a systematic review of the genomics, transcriptomics, proteomics and metabolomics associated with Salvia miltiorrhiza, summarized the advances in biosynthesis, regulation and related functional genes, and also put forward some scientific problems of Salvia miltiorrhiza that need to be further studied in the future.
Key words:    Salvia miltiorrhiza    active ingredient    biosynthesis and regulation    multi-omics approach   
收稿日期: 2020-08-07
DOI: 10.16438/j.0513-4870.2020-1300
通讯作者: 詹忠根,Tel:86-571-86929836,E-mail:zhzg9321@163.com
Email: zhzg9321@163.com
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参考文献:
[1] Wang QW, Dai XX, Xiang X, et al. Advances in the molecular mechanism of salvianolic acid and tanshinone for intervention of diabetic kidney disease[J]. Acta Pharm Sin (药学学报), 2019, 54:1356-1363.
[2] Song JY, Luo HM, Li CF, et al. Salvia miltiorrhiza as medicinal model plant[J]. Acta Pharm Sin (药学学报), 2013, 48:1099-1106.
[3] Wang QR, Li XY, Sun Y, et al. Research on distribution of tanshinones in different parts of danshen's root by raman spectroscopy[J]. J Light Scattering (光散射学报), 2018, 30:351-356.
[4] Duan ZQ, Liu YY, Zheng XJ, et al. A study on distribution characteristics of tanshinone ⅡA and salvianolic acid B in root tissues of Salvia miltiorrhiza[J]. J Henan Agric Univ (河南农业大学学报), 2007, 41:178-182.
[5] Sha XX, Su SL, Shen F, et al. Distribution of salvianolic acids in aerial parts of Salvia miltiorrhiza during different growing periods and accumulation dynamic analysis[J]. Chin Tradit Herb Drugs(中草药), 2015, 46:3414-3419.
[6] Zhang GH, Tian Y, Zhang J, et al. Hybrid de novo genome assembly of the Chinese herbal plant danshen (Salvia miltiorrhiza Bunge)[J]. Giga Sci, 2015, 4:62-65.
[7] Xu HB, Song JY, Luo HM, et al. Analysis of the genome sequence of the medicinal plant Salvia miltiorrhiza[J]. Mol Plant, 2016, 9:949-952.
[8] Qian J, Song JY, Gao HH, et al. The complete chloroplast genome sequence of the medicinal plant Salvia miltiorrhiza[J]. PLoS One, 2013, 8:e57607.
[9] Chen HM, Zhang JH, Yuan G, et al. Complex interplay among DNA modification, noncoding RNA expression and protein-coding RNA expression in Salvia miltiorrhiza chloroplast genome[J]. PLoS One, 2014, 9:e99314.
[10] Wu B, Chen HM, Shao JJ, et al. Identification of symmetrical RNA editing events in the mitochondria of Salvia miltiorrhiza by strand-specific RNA sequencing[J]. Sci Rep, 2017, 7:42250-42260.
[11] Qian J. Study on Chloroplast and Mitochondrial Genomes of Salvia miltiorrhiza (丹参的叶绿体和线粒体基因组研究)[D]. Beijing:Chinese Academy of Medical Sciences & Peking Union Medcal College, 2014.
[12] Cui GH, Huang LQ, Tang XJ, et al. Functional genomics studies of Salvia miltiorrhiza I. establish cDNA microarray of S. miltiorrhiza[J]. China J Chin Mater Med (中国中药杂志), 2007, 32:1137-1141.
[13] Shao YX, Wei JB, Wu FL, et al. DsTRD:Danshen transcriptional resource database[J]. PLoS One, 2016, 11:e0149747.
[14] Zhou W, Huang Q, Wu X, et al. Comprehensive transcriptome profiling of Salvia miltiorrhiza for discovery of genes associated with the biosynthesis of tanshinones and phenolic acids[J]. Sci Rep, 2017, 7:10554-10565.
[15] Li HQ, Li CL, Deng YX, et al. The pentatricopeptide repeat gene family in Salvia miltiorrhiza:genome-wide characterization and expression analysis[J]. Molecules, 2018, 23:1364-1375.
[16] Wang XY. The Analysis of Expression and Biosynthesis Gene Cloning of Active Components from Hairy Root of Salvia miltiorrhiza (丹参毛状根基因诱导表达分析及其有效成分生物合成基因的克隆研究)[D]. Beijing:China Academy of Chinese Medical Sciences, 2007.
[17] Luo HM, Zhu YJ, Song JY, et al. Transcriptional data mining of Salvia miltiorrhiza in response to methyl jasmonate to examine the mechanism of bioactive compound biosynthesis and regulation[J]. Physiol Plant, 2014, 152:241-255.
[18] Yan Y, Wang Z, Tian W, et al. Generation and analysis of expressed sequence tags from the medicinal plant Salvia miltiorrhiza [J]. Sci China Life Sci, 2010, 53:273-285.
[19] Li Y, Sun C, Luo HM, et al. Transcriptome characterization for Salvia miltiorrhiza using 454 GSFLX[J]. Acta Pharm Sin (药学学报), 2010, 45:524-529.
[20] Hua WP, Zhang Y, Song J, et a1. De novo transcriptome sequencing in Salvia miltiorrhiza to identify genes involved in the biosynthesis ofactive ingredients[J]. Genomics, 2011, 98:272-279.
[21] Yang L, Ding GH, Lin HY, et al. Transcriptome analysis of medicinal plant Salvia miltiorrhiza and identification of genes related to tanshinone biosynthesis[J]. PLoS One, 2013, 8:e80464.
[22] Xu ZC, Peters RJ, Weirather J, et al. Full-length transcriptome sequences and splice variants obtained by a combination of sequencing platforms applied to different root tissues of Salvia miltiorrhiza and tanshinone biosynthesis[J]. Plant J, 2015, 82:951-961.
[23] Xu ZC, Luo HM, Ji AJ, et al. Global identification of the full-length transcripts and alternative splicing related to phenolic acid biosynthetic genes in Salvia miltiorrhiza[J]. Front Plant Sci, 2016, 7:100-109.
[24] Wang YJ, Shen Y, Shen Z, et al. Comparative proteomic analysis of the response to silver ions and yeast extract in Salvia miltiorrhiza hairy root cultures[J]. Plant Physiol Biochem, 2016, 107:364-373.
[25] Contreras A, Leroy B, Mariage PA, et al. Proteomic analysis reveals novel insights into tanshinones biosynthesis in Salvia miltiorrhiza hairy roots[J]. Sci Rep, 2019, 9:5768-5780.
[26] Wang RH, Lu CY, Shu ZM, et al. iTRAQ-based proteomic analysis reveals several key metabolic pathways associated with male sterility in Salvia miltiorrhiza[J]. RSC Adv, 2020, 10:16959-16970.
[27] Jiang MM, Wang CH, Zhang Y, et al. Sparse partial-least-squares discriminant analysis for different geographical origins of Salvia miltiorrhiza by 1H-NMR-based metabolomics[J]. Phytochem Anal, 2014, 25:50-58.
[28] Zhao Q, Song ZQ, Fang XS, et al. Effect of genotype and environment on Salvia miltiorrhiza roots using LC/MS-based metabolomics[J]. Molecules, 2016, 21:414-430.
[29] Gao W, Sun H X, Xiao H, et al. Combining metabolomics and transcriptomics to characterize tanshinone biosynthesis in Salvia miltiorrhiza[J]. BMC Genomics, 2014, 15:73-86.
[30] Jiang Y, Wang L, Lu SR, et al. Transcriptome sequencing of Salvia miltiorrhiza after infection by its endophytic fungi and identification of genes related to tanshinone biosynthesis[J]. Pharm Biol, 2019, 57:1-11.
[31] Zhan ZL, Fang WT, Ma XH, et al. Metabolome and transcriptome analyses reveal quality change in the orange‑rooted Salvia miltiorrhiza (Danshen) from cultivated field[J]. Chin Med, 2019, 14:42-51.
[32] Liu BX, Jin MX, Zhang M, et al. The application of combined 1H NMR-based metabolomics and transcriptomics techniques to explore phenolic acid biosynthesis in Salvia miltiorrhiza[J]. J Pharm Biomed Anal, 2019, 172:126-138.
[33] Ge Q, Zhang Y, Hua WP, al et,Combination of transcriptomic and metabolomic analyses reveals a JAZ repressor in the jasmonate signaling pathway of Salvia miltiorrhiza [J]. Sci Rep, 2015, 5:14048-14061.
[34] Wu SJ, Shi M, Wu JY. Cloning and characterization of the 1-deoxy-D-xylulose 5-phosphate reductoisomerase gene for diterpenoid tanshinone biosynthesis in Salvia miltiorrhiza (Chinese sage) hairy roots[J]. Biotechnol Appl Biochem, 2009, 52:89-95.
[35] Liao P, Zhou W, Zhang L, et al. Molecular cloning, characterization and expression analysis of a new gene encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase from Salvia miltiorrhiza[J]. Acta Physiol Plant, 2009, 31:565-572.
[36] Wang X, Cui G, Huang L, et al. A full length cDNA of 4-(cytidine 5'-2 diphospho)-2-C-methyl-D-erythritol kinase cloning and analysis of introduced gene expression in Salvia miltiorrhiza[J]. Acta Pharm Sin (药学学报), 2010, 43, 1251-1257.
[37] Kai GY, Liao P, Zhang T, et al. Characterization, expression profiling, and functional identification of a gene encoding geranylgeranyl diphosphate synthase from Salvia miltiorrhiza[J]. Biotechnol Bioproc Eng, 2010, 15:236-245.
[38] Cui G, Huang L, Tang X, et al. Candidate genes involved in tanshinone biosynthesis in hairy roots of Salvia miltiorrhiza revealed by cDNA microarray[J]. Mol Biol Rep, 2011, 38:2471-2478.
[39] Dai ZB, Cui GH, Zhou SF, et al. Cloning and characterization of a novel 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Salvia miltiorrhiza involved in diterpenoid tanshinone accumulation[J]. J Plant Physiol, 2011, 168:148-157.
[40] Ma YM, Yuan LC, Wu B, et al. Genome-wide identification and characterization of novel genes involved in terpenoid biosynthesis in Salvia miltiorrhiza[J]. J Exp Bot, 2012, 63:2809-2823.
[41] Shi M, Luo XQ, Ju GH, et al. Enhanced diterpene tanshinone accumulation and bioactivity of transgenic Salvia miltiorrhiza hairy roots by pathway engineering[J]. J Agric Food Chem, 2016, 64:2523-2530.
[42] Gao W, Hillwig ML, Huang L, et al. A functional genomics approach to tanshinone biosynthesis provides stereochemical insights[J]. Org Lett, 2009, 11:5170-5173.
[43] Cui G, Duan L, Jin B, et al. Functional divergence of diterpene syntheses in the medicinal plant Salvia miltiorrhiza Bunge[J]. Plant Physiol, 2015, 169:1607-1618.
[44] Cheng Q, Su P, Hu Y, et al. RNA interference-mediated repression of SmCPS expression in hairy roots of Salvia miltiorrhiza causes a decrease of tanshinones and sheds light on the functional role of SmCPS[J]. Biotechnol Lett, 2014, 36:363-369.
[45] Bai ZQ, Liu JL, Zhang CL, et al. Coding single nucleotide polymorphisms and SmCPS1 and SmKSL1 subcellular localization are associated with tanshinone biosynthesis in Salvia miltiorrhiza Bunge roots[J]. Acta Physiol Plant, 2018, 40:6-16.
[46] Guo J, Zhou YJ, Hillwig L, et al. CYP76AH1catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts[J]. Proc Natl Acad Sci U S A, 2013, 110:12108-12113.
[47] Guo J, Ma XH, Cai Y, et al. Cytochrome P450 promiscuity leads to a bifurcating biosynthetic pathway for tanshinones[J]. New Phytologist, 2016, 210:525-534.
[48] Chen H, Wu B, Nelson DR, et al. Computational identification and systematic classification of novel cytochrome 450 genes in Salvia miltiorrhiza[J]. PLoS One, 2014, 9:e115149.
[49] Xu Z, Song J. The 2-oxoglutarate-dependent dioxygenase superfamily participates in tanshinone production in Salvia miltiorrhiza[J]. J Exp Bot, 2017, 68:2299-2308.
[50] Mizutani M, Sato F. Unusual P450 reactions in plant secondary metabolism[J]. Arch Biochem Biophys, 2011, 507:194-203.
[51] Chang YJ, Wang MZ, Li J, et al. Transcriptomic analysis reveals potential genes involved in tanshinone biosynthesis in Salvia miltiorrhiza[J]. Sci Rep, 2019, 9:14929.
[52] Renault H, Bassard JE, Hamberger B, et al. Cytochrome P450-mediated metabolic engineering:current progress and future challenges[J]. Curr Opin Plant Biol, 2014, 19:27-34.
[53] Bak S, Beisson F, Bishop G, et al. Cytochromes P450//in Arabidopsis Book[M]. Rockville:American Society of Plant Biologists, 2011, 9:e0144.
[54] Petersen M, Häusler E, Karwatzki B, et al. Proposed biosynthetic pathway for rosmarinic acid in cell cultures of Coleus blumei Benth[J]. Planta, 1993, 189:10-14.
[55] Di P. Exploring the Biosynthetic Pathway of Phenolic Acids and Functional Study of the Involved Genes in Salvia miltiorrhiza Bunge (丹参酚酸类成分生源途径的探索及相关基因的克隆与功能研究)[D]. Shanghai:Second Military Medical University, 2012.
[56] Di P, Zhang L, Chen JF, et al. C13 tracer reveals phenolic acids biosynthesis in hairy root cultures of Salvia miltiorrhiza[J]. ACS Chem Biol, 2013, 8:1537-1548.
[57] Song J, Wang Z. Molecular cloning, expression and characterization of a phenylalanine ammonia-lyase gene (SmPAL1) from Salvia miltiorrhiza[J]. Mol Biol Rep, 2009, 36:939-952.
[58] Song J, Wang ZZ. RNAi-mediated suppression of the phenylalanine ammonia-lyase gene in Salvia miltiorrhiza causes abnormal phenotypes and a reduction in rosmarinic acid biosynthesis[J]. J Plant Res, 2011, 124:183-192.
[59] Huang B, Duan Y, Yi B, et al. Characterization and expression profiling of cinnamate 4-hydroxylase gene from Salvia miltiorrhiza in rosmarinic acid biosynthesis pathway[J]. Russ J Plant Physiol, 2008, 55:390-399.
[60] Zhao SJ, Hu ZB, Liu D, et al. Two divergent members of 4-coumarate:coenzyme A ligase from Salvia miltiorrhiza Bunge:cDNA cloning and functional study[J]. J Integr Plant Biol, 2006, 48:1355-1364.
[61] Huang BB, Yi B, Duan YB, et al. Characterization and expression profiling of tyrosine aminotransferase gene from Salvia miltiorrhiza (Dan-shen) in rosmarinic acid biosynthesis pathway[J]. Mol Biol Rep, 2008, 35:601-612.
[62] Xiao Y, Zhang L, Gao SH, et al. The C4H, TAT, HPPR and HPPD genes prompted engineering of rosmarinic acid biosynthetic pathway in Salvia miltiorrhiza hairy root cultures[J]. PLoS One, 2011, 6:e29713.
[63] Xiao Y, Di P, Chen JF, et al. Characterization and expression profiling of 4-hydroxyphenylpyruvate dioxygenase gene (SmHPPD) from Salvia miltiorrhiza hairy root cultures[J]. Mol Biol Rep, 2009, 36:2019-2029.
[64] Wang B, Sun W, Li QS, et al. Genome-wide identification of phenolic acid biosynthetic genes in Salvia miltiorrhiza[J]. Planta, 2014, 241:711-725.
[65] Song J, Ji YY, Xu K, et al. An integrated analysis of the rosmarinic acid-biosynthetic genes to uncover the regulation of rosmarinic acid pathway in Salvia miltiorrhiza[J]. Acta Physiol Plant, 2012, 34:1501-1511.
[66] Li Q, Feng JX, Chen L, et al. Genome-wide identification and characterization of Salvia miltiorrhiza laccases reveal potential targets for salvianolic acid B biosynthesis[J]. Front Plant Sci, 2019, 10:435-449.
[67] Xiao Y, Gao SH, Di P, et al. Lithospermic acid B is more responsive to silver ions (Ag+) than rosmarinic acid in Salvia miltiorrhiza hairy root cultures[J]. Biosci Rep, 2010, 30:33-40.
[68] Xing BC, Yang DF, Guo WL, et al. Ag+ as a more effective elicitor for production of tanshinones than phenolic acids in Salvia miltiorrhiza hairy roots[J]. Molecules, 2015, 20:309-324.
[69] Guo YX, Zhang DJ, Wang H, et al. Hydrolytic kinetics of lithospermic acid B extracted from roots of Salvia miltiorrhiza[J]. J Pharm Biomed Anal, 2007, 43:435-439.
[70] Zhang SC, Yan Y, Wang BQ, et al. Selective responses of enzymes in the two parallel pathways of rosmarinic acid biosynthetic pathway to elicitors in Salvia miltiorrhiza hairy root cultures[J]. J Biosci Bioeng, 2014, 117:645-651.
[71] Jiang BH, Li DF, Deng YP, et al. Salvianolic acid A, a novel matrix metalloproteinase-9 inhibitor, prevents cardiac remodeling in spontaneously hypertensive rats[J]. PLoS One, 2013, 8:e59621.
[72] Cao J, Wei YJ, Qi LW, et al. Determination of fifteen bioactive components in Radixet Rhizoma Salviae Miltiorrhizae by high-performance liquid chromatography with ultraviolet and mass spectrometric detection[J]. Biomed Chromatogr, 2008, 22:164-172.
[73] Pei TL, Ma PD, Ding K, et al. SmJAZ8 acts as a core repressor regulating JA-induced biosynthesis of salvianolic acids and tanshinones in Salvia miltiorrhiza hairy roots[J]. J Exp Bot, 2018, 69:1663-1678.
[74] Zhang X, Luo HM, Xu ZC, et al. Genome-wide characterisation and analysis of bHLH transcription factors related to tanshinone biosynthesis in Salvia miltiorrhiza[J]. Sci Rep, 2015, 5:11244.
[75] Yang N, zhou WP, Su J, et al. Overexpression of SmMYC2 increases the production of phenolic acids in Salvia miltiorrhiza[J]. Front Plant Sci, 2017, 8:1804-1815.
[76] Xing BC, Yang DF, Yu HZ, et al. Overexpression of SmbHLH10 enhances tanshinones biosynthesis in Salvia miltiorrhiza hairy roots[J]. Plant Sci, 2018, 276:229-238.
[77] Cao WZ. The Functional Study of SmbHLH 7 Transcription Factor in Salvia miltiorrhiza (丹参SmbHLH7转录因子的克隆与功能初探)[D]. Shanghai:Shanghai Normal University, 2018.
[78] Zhu XY. Study on the Regulation of SmMYB4 on the Synthesis of Secondary Metabolites in Salvia miltiorrhiza (SmMYB4对丹参次生代谢产物合成的调节作用研究)[D]. Xi'an:Shaanxi Normal University, 2016.
[79] Liu L, Yang DF, Xing BC, et al. SmMYB98b positive regulation to tanshinones in Salvia miltiorrhiza Bunge hairy roots[J]. Plant Cell Tissue Organ Culture, 2020, 140:459-467.
[80] Zhang J, Zhou L, Zheng X, et al. Overexpression of SmMYB9b enhances tanshinone concentration in Salvia miltiorrhiza hairy roots[J]. Plant Cell Rep, 2017, 36:1297-1309.
[81] Hao XL, Pu ZQ, Cao G, et al. Tanshinone and salvianolic acid biosynthesis are regulated by SmMYB98 in Salvia miltiorrhiza hairy roots[J]. J Adv Res, 2020, 23:1-12.
[82] Li CL, Li DQ, Shao FJ, et al. Molecular cloning and expression analysis of WRKY transcription factor genes in Salvia miltiorrhiza[J]. BMC Genomics, 2015, 16:200-220.
[83] Yu HZ, Guo WL, Yang DF, et al. Transcriptional profiles of SmWRKY family genes and their putative roles in the biosynthesis of tanshinone and phenolic acids in Salvia miltiorrhiza[J]. Int J Mol Sci, 2018, 19:1593-1609.
[84] Cao WZ, Wang Y, Shi M, et al. Transcription factor SmWRKY1 positively promote the biosynthesis of tanshinones in Salvia miltiorrhiza[J]. Front Plant Sci, 2018, 9:554-563.
[85] Deng CP, Hao XL, Shi M, et al. Tanshinone production could be increased by the expression of SmWRKY2 in Salvia miltiorrhiza hairy roots[J]. Plant Sci, 2019, 284:1-8.
[86] Li LL. Preliminary Study on the Function of SmWRKY54 Transcription Factor in Salvia miltiorrhiza (丹参SmWRKY54转录因子功能初步研究)[D]. Shanghai:Shanghai Normal University, 2016.
[87] Hao XR. The Function Study of SmWRKY3 and SmWRKY70 Transcription Factors in Salvia miltiorrhiza (丹参SmWRKY3和SmWRKY70转录因子功能研究)[D]. Shanghai:Shanghai Normal University, 2014.
[88] Zhang XC. The Functional Study of SmWRKY9 Transcription Factor in Salvia miltiorrhiza (丹参SmWRKY9转录因子功能研究)[D]. Shanghai:Shanghai Normal University, 2019.
[89] Wang LR. Identification of GRAS Transcription Factor Family and Study on the Function of DELLA Subfamily Gene in Salvia miltiorrhiza (丹参GRAS转录因子家族鉴定及DELLA亚家族基因功能研究)[D]. Xi'an:Shaanxi Normal University, 2018.
[90] Huang Q. Isolation and Functional Analysis of Two ERF Transcription Factors in Salvia miltiorrhiza (丹参两个ERF类转录因子的克隆与功能分析)[D]. Shanghai:Shanghai Normal University, 2015.
[91] Huang Q, Sun MH, Yuan TP, et al. The AP2/ERF transcription factor SmERF1L1 regulates the biosynthesis of tanshinones and phenolic acids in Salvia miltiorrhiza[J]. Food Chem, 2019, 274:368-375.
[92] Bai ZQ, Li WR, Jia YY, et al. The ethylene response factor SmERF6 co-regulates the transcription of SmCPS1 and SmKSL1and is involved in tanshinone biosynthesis in Salvia miltiorrhiza hairy roots[J]. Planta, 2018, 248:243-255.
[93] Zhang Y, Ji AJ, Xu ZC, et al. The AP2/ERF transcription factor SmERF128 positively regulates diterpenoid biosynthesis in Salvia miltiorrhiza[J]. Plant Mol Biol, 2019, 100:83-93.
[94] Sun M, Shi M, Wang Y, et al. The biosynthesis of phenolic acids is positively regulated by the JA-responsive transcription factor ERF115 in Salvia miltiorrhiza[J]. J Exp Bot, 2019, 70:243-254.
[95] Lu XY, Liang XY, Li X, et al. Genome-wide characterisation and expression profiling of the LBD family in Salvia miltiorrhiza reveals the function of LBD50 in jasmonate signaling and phenolic biosynthesis[J]. Ind Crops Prod, 2020, 144:112006-112019.
[96] Xu XB, Jiang QH, Ma XY, et al. Deep sequencing identifies tissue-specific microRNAs and their target genes involving in the biosynthesis of tanshinones in Salvia miltiorrhiza [J]. PLoS One, 2014, 9:e111679.
[97] Zhang LS, Wu B, Zhao DG, et al. Genome-wide analysis and molecular dissection of the SPL gene family in Salvia miltiorrhiza [J]. J Intrgr Plant Biol, 2014, 56:38-50.
[98] Xu ZH, Ji AJ, Song JY, et al. Genome-wide analysis of auxin response factor gene family members in medicinal model plant Salvia miltiorrhiza[J]. Biol Open, 2016, 5:848-857.
[99] Yu HZ, Jiang MD, Xing BC, et al. Systematic analysis of Kelch Repeat F-box (KFB) protein gene family and identification of phenolic acid regulation members in Salvia miltiorrhiza Bunge[J]. Genes, 2020, 11:557-572.
[100] Li DQ, Shao FJ, Lu SF, et al. Identification and characterization of mRNA-like noncoding RNAs in Salvia miltiorrhiza[J]. Planta, 2015, 241:1131-1143.
[101] Shao FJ, Lu SF. Genome-wide identification, molecular cloning, expression profiling and posttranscriptional regulation analysis of the Argonaute gene family in Salvia miltiorrhiza, an emerging model medicinal plant[J]. BMC Genomics, 2013, 14:512.
[102] Shao FJ, Lu SF, Zhang BH. Identification, molecular cloning and expression analysis of five RNA-dependent RNA polymerase genes in Salvia miltiorrhiza[J]. PLoS One, 2014, 9:e95117.
[103] Song ZQ, Guo LL, Liu T, et al. Comparative RNA-sequence transcriptome analysis of phenolic acid metabolism in Salvia miltiorrhiza, a traditional Chinese medicine model plant[J]. Int J Genomics, 2017, 2017:9364594.
[104] Du Q, Li CL, Li DQ, et al. Genome-wide analysis, molecular cloning and expression profiling reveal tissuespecifically expressed, feedback-regulated, stress-responsive and alternatively spliced novel genes involved in gibberellin metabolism in Salvia miltiorrhiza[J]. BMC Genomics, 2015, 16:1087-1108.
[105] Wang HB, Wei T, Wang X, et al. Transcriptome analyses from mutant Salvia miltiorrhiza reveals important roles for SmGASA4 during plant development[J]. Int J Mol Sci, 2018, 19:2088-2108.
[106] Deng YX, Li CL, Li HQ, et al. Identification and characterization of flavonoid biosynthetic enzyme genes in Salvia miltiorrhiza (Lamiaceae)[J]. Molecules, 2018, 23:1467-1485.
[107] Li YH. Cloning and Functional Analysis of the Key Enzyme Genes Involved in the Flavonoids Biosynthesis in Salvia miltiorrhiza (丹参类黄酮合成途径关键酶基因的克隆与功能分析)[D]. Yangling:Northwest A&F University, 2019.