Skip to main content

Genetic Engineering and Manipulation of Metabolite Pathways in Salvia Spp.

  • Chapter
  • First Online:
Salvia Biotechnology
  • 743 Accesses

Abstract

Plants from the genus Salvia have been recognized as medicinal herbs all over the world since earliest times. They are known to accumulate diverse range of bioactive phytochemicals, including polyphenols (rosmarinic and salvianolic acids), triterpenes (ursolic and oleanolic acids), diterpenes (tanshinones, carnosic acid), flavonoids and sterols, etc. Nowadays, the powerful methods of genetic and metabolic engineering, synthetic biology and combinatorial biosynthesis have been widely applied for improvement of commercial crops yields and for increasing their medicinal value by modulating the accumulation of biologically active phytochemicals. Over the past few years, these techniques have been applied in Salvia plants and in vitro systems, but the research still remains limited to few species. In this chapter, we summarized the recent achievements in genetic engineering of Salvia species, with special attention on metabolite engineering of phenolic biosynthesis and terpenoids biosynthesis pathways. Some aspects of the applications of functional genes, cloned by Salvia species, for the needs of synthetic biology and combinatorial biosynthesis are reviewed as well.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

GRAS:

Generally recognized as safe

FDA:

Food and drug administration

EMA:

European medicines agency

NCBI:

National center for biotechnology information

CDS:

Coding DNA sequence

EST:

Expressed sequence tags

DNA:

Deoxyribonucleic acid

cDNA:

complementary DNA

nrITS:

nuclear internal transcribed spacer

CaMV35S:

Cauliflower mosaic virus 35S promoter

hptII :

hygromycin phosphotransferase gene

ATM:

Activation tagging mutagenesis

T-DNA:

Transferred DNA

LEA:

Late embryogenesis abundant

AtDREB:

Arabidopsis thaliana dehydration-responsive-element-binding protein

SAMDC:

S-adenosylmethionine decarboxylase

AtEDT:

Arabidopsis thaliana-enhanced drought tolerance

R2R3-MYB:

R2R3 type -myeloblastosis protein

WRKY:

WRKY transcription factor

C4H:

Cinnamic acid 4-hydroxylase

TAT:

Tyrosine aminotransferase

PAL:

Phenylalanine ammonialyase

4CL:

4-Coumaroyl:CoA ligase

HPPR:

4-Hydroxyphenylpyruvate reductase

CYP:

Cytochrome P450 reductase

RAS:

Rosmarinic acid synthase

RNA:

Ribonucleic acid

mRNA:

messenger RNA

RNAi:

RNA interference

AtPAP:

Arabidopsis thaliana production of anthocyanin pigment

CCR:

Cinnamoyl-CoA reductase

COMT:

Caffeic acid O-methyltransferase

MEP:

Methyl-d-erythritol 4-phosphate pathway

MVA:

Mevalonic acid pathway

DXS:

1-Deoxy-d-xylulose 5-phosphate synthase

DXP:

1-Deoxy-d-xylulose 5-phosphate

MCT:

2-C-methyl-d-erythritol 4-phosphate cytidylyltransferase

CMK:

4-(cytidine 5′-diphospho)-2-C-methyl-d-erythritol kinase

MDS:

2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase

HDS:

4-hydroxy-3-methylbut-2-enyl diphosphate synthase

HDR:

4-hydroxy-3-methylbut-2-enyl diphosphate reductase

GPS:

Geranyl diphosphate synthase

GGPS:

Geranylgeranyl diphosphate synthase

PSY:

Phytoene synthase

AACT:

Acetyl-CoA C-acetyltransferase

HMGS:

Hydroxymethylglutaryl-CoA synthase

HMGR:

Hydroxymethylglutaryl-CoA reductase

MK:

Mevalonate kinase

PMK:

5-Phosphomevalonate kinase

MDK:

Mevalonate pyrophosphate decarboxylase

SQS:

Squalene synthase

FPS:

Farnesyl diphosphate synthase

IDI:

Isopentenyl diphosphate isomerase

bHLH:

basic helix-loop-helix

GSG:

Gly-Ser repeats linker

References

  1. Scholey A, Camfield D, Owen L, Pipingas A, Stough C (2011) Functional foods and cognition In: Saarela M (ed) Functional Foods, 2nd edn. Woodhead Publishing, pp 277–308. https://doi.org/10.1533/9780857092557.2.277

  2. Berdahl DR, McKeague J (2015) Rosemary and sage extracts as antioxidants for food preservation. In: Shahidi F (ed) Handbook of antioxidants for food preservation. Woodhead Publishing, pp 177–217. https://doi.org/10.1016/B978-1-78242-089-7.00008-7

  3. Doğan S, Turan P, Doğan M, Arslan O, Alkan M (2007) Variations of peroxidase activity among Salvia species. J Food Eng 79(2):375–382. https://doi.org/10.1016/j.jfoodeng.2006.02.001

    Article  Google Scholar 

  4. Panda H (2005) Cultivation and utilization of aromatic plants. Asia Pacific Business Press INC., Delhi

    Google Scholar 

  5. Tissier A (2012) Trichome specific expression: promoters and their applications. In: Çiftçi YÖ (ed) Transgenic plants-advances and limitations. InTech, pp 353–378. https://doi.org/10.5772/32101

  6. Ullah R, Nadeem M, Khalique A, Imran M, Mehmood S, Javid A, Hussain J (2016) Nutritional and therapeutic perspectives of Chia (Salvia hispanica L.): a review. J Food Sci Technol 53(4):1750–1758. https://doi.org/10.1007/s13197-015-1967-0

    Article  CAS  PubMed  Google Scholar 

  7. Zhou L, Zuo Z, Chow MSS (2005) Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J Clin Pharmacol 45(12):1345–1359. https://doi.org/10.1177/0091270005282630

    Article  CAS  PubMed  Google Scholar 

  8. Bücheler R, Gleiter CH, Schwoerer P, Gaertner I (2005) Use of nonprohibited hallucinogenic plants: increasing relevance for public health? A case report and literature review on the consumption of Salvia divinorum. Pharmacopsychiatry 38(1):1–5. https://doi.org/10.1055/s-2005-837763

    Article  PubMed  Google Scholar 

  9. United States Food and Drug Administration (FDA) (2011) 21 CFR Part 582.20. Substances Generally Recognized as Safe. National Archives and Records Administration, Washington, DC

    Google Scholar 

  10. European Directorate for the Quality of Medicines (2010) European Pharmacopoeia, 7th edn (PhEur 7.0). European Pharmacopoeia Commission, Strasbourg, France

    Google Scholar 

  11. Mohd Ali N, Yeap SK, Ho WY, Beh BK, Tan SW, Tan SG (2012) The promising future of Chia, Salvia hispanica L. J Biomed Biotechnol 2012:9. https://doi.org/10.1155/2012/171956

    Article  Google Scholar 

  12. Benkeblia N (2017) Phytonutritional improvement of crops. Wiley-Blackwell, NJ

    Book  Google Scholar 

  13. Walker JB, Sytsma KJ, Treutlein J, Wink M (2004) Salvia (Lamiaceae) is not monophyletic: implications for the systematics, radiation, and ecological specializations of Salvia and tribe Mentheae. Am J Bot 91(7):1115–1125. https://doi.org/10.3732/ajb.91.7.1115

    Article  PubMed  Google Scholar 

  14. Will M, Claßen-Bockhoff R (2017) Time to split Salvia s.l. (Lamiaceae)—new insights from old world Salvia phylogeny. Mol Phylogenet Evol 109:33–58. https://doi.org/10.1016/j.ympev.2016.12.041

    Article  PubMed  Google Scholar 

  15. Wenping H, Yuan Z, Jie S, Lijun Z, Zhezhi W (2011) De novo transcriptome sequencing in Salvia miltiorrhiza to identify genes involved in the biosynthesis of active ingredients. Genomics 98(4):272–279. https://doi.org/10.1016/j.ygeno.2011.03.012

    Article  PubMed  Google Scholar 

  16. Yang L, Ding G, Lin H, Cheng H, Kong Y, Wei Y, Fang X, Liu R, Wang L, Chen X, Yang C (2013) Transcriptome analysis of medicinal plant Salvia miltiorrhiza and Identification of Genes Related to Tanshinone Biosynthesis. PLoS ONE 8(11):e80464. https://doi.org/10.1371/journal.pone.0080464

    Article  PubMed  PubMed Central  Google Scholar 

  17. Gao W, Sun H-X, Xiao H, Cui G, Hillwig ML, Jackson A, Wang X, Shen Y, Zhao N, Zhang L, Wang X-J, Peters RJ, Huang L (2014) Combining metabolomics and transcriptomics to characterize tanshinone biosynthesis in Salvia miltiorrhiza. BMC Genom 15(1):73. https://doi.org/10.1186/1471-2164-15-73

    Article  Google Scholar 

  18. Song Z, Guo L, Liu T, Lin C, Wang J, Li X (2017) Comparative RNA-sequence transcriptome analysis of phenolic acid metabolism in Salvia miltiorrhiza, a traditional Chinese medicine model plant. Int J Genomics 2017:10. https://doi.org/10.1155/2017/9364594

    Article  Google Scholar 

  19. Qian J, Song J, Gao H, Zhu Y, Xu J, Pang X, Yao H, Sun C, Xe Li, Li C, Liu J, Xu H, Chen S (2013) The complete chloroplast genome sequence of the medicinal plant Salvia miltiorrhiza. PLoS ONE 8(2):e57607. https://doi.org/10.1371/journal.pone.0057607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Xu H, Song J, Luo H, Zhang Y, Li Q, Zhu Y, Xu J, Li Y, Song C, Wang B, Sun W, Shen G, Zhang X, Qian J, Ji A, Xu Z, Luo X, He L, Li C, Sun C, Yan H, Cui G, Li X, Xe Li, Wei J, Liu J, Wang Y, Hayward A, Nelson D, Ning Z, Peters Reuben J, Qi X, Chen S (2016) Analysis of the genome sequence of the medicinal plant Salvia miltiorrhiza. Mol Plant 9(6):949–952. https://doi.org/10.1016/j.molp.2016.03.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Xu Z, Luo H, Ji A, Zhang X, Song J, Chen S (2016) Global identification of the full-length transcripts and alternative splicing related to phenolic acid biosynthetic genes in Salvia miltiorrhiza. Front Plant Sci 7(100). https://doi.org/10.3389/fpls.2016.00100

  22. Ho H-S, Vishwakarma RK, Chen EC-F, Tsay H-S (2013) Activation tagging in Salvia miltiorrhiza can cause increased leaf size and accumulation of tanshinone I and IIA in its roots. Botanical Studies 54:37. https://doi.org/10.1186/1999-3110-54-37

  23. Wu Y, Liu C, Kuang J, Ge Q, Zhang Y, Wang Z (2014) Overexpression of SmLEA enhances salt and drought tolerance in Escherichia coli and Salvia miltiorrhiza. Protoplasma 251(5):1191–1199. https://doi.org/10.1007/s00709-014-0626-z

    Article  CAS  PubMed  Google Scholar 

  24. Liu Y, Sun G, Zhong Z, Zheng X, Deng K (2017) Overexpression of SAMDC gene from Salvia miltiorrhiza enhances drought tolerance in transgenic tobacco (Nicotiana tabacum). J Agric Biotechnol 25(5):729–738

    Google Scholar 

  25. Wei T, Deng K, Liu D, Gao Y, Liu Y, Yang M, Zhang L, Zheng X, Wang C, Song W, Chen C, Zhang Y (2016) Ectopic expression of DREB transcription factor, AtDREB1A, confers tolerance to drought in transgenic Salvia miltiorrhiza. Plant Cell Physiol 57(8):1593–1609. https://doi.org/10.1093/pcp/pcw084

    Article  CAS  PubMed  Google Scholar 

  26. Wei T, Deng K, Gao Y, Liu Y, Yang M, Zhang L, Zheng X, Wang C, Song W, Chen C, Zhang Y (2016) Arabidopsis DREB1B in transgenic Salvia miltiorrhiza increased tolerance to drought stress without stunting growth. Plant Physiol Biochem 104(Supplement C):17–28. https://doi.org/10.1016/j.plaphy.2016.03.003

  27. Wei T, Deng K, Zhang Q, Gao Y, Liu Y, Yang M, Zhang L, Zheng X, Wang C, Liu Z, Chen C, Zhang Y (2017) Modulating AtDREB1C expression improves drought tolerance in Salvia miltiorrhiza. Front Plant Sci 8(52). https://doi.org/10.3389/fpls.2017.00052

  28. Liu Y, Sun G, Zhong Z, Ji L, Zhang Y, Zhou J, Zheng X, Deng K (2017) Overexpression of AtEDT1 promotes root elongation and affects medicinal secondary metabolite biosynthesis in roots of transgenic Salvia miltiorrhiza. Protoplasma 254(4):1617–1625. https://doi.org/10.1007/s00709-016-1045-0

    Article  CAS  PubMed  Google Scholar 

  29. Li C, Lu S (2014) Genome-wide characterization and comparative analysis of R2R3-MYB transcription factors shows the complexity of MYB-associated regulatory networks in Salvia miltiorrhiza. BMC Genom 15(1):277. https://doi.org/10.1186/1471-2164-15-277

    Article  Google Scholar 

  30. Li C, Li D, Shao F, Lu S (2015) Molecular cloning and expression analysis of WRKY transcription factor genes in Salvia miltiorrhiza. BMC Genom 16(1):200. https://doi.org/10.1186/s12864-015-1411-x

    Article  Google Scholar 

  31. Zhang S, Ma P, Yang D, Li W, Liang Z, Liu Y, Liu F (2013) Cloning and characterization of a putative R2R3 MYB transcriptional repressor of the rosmarinic acid biosynthetic pathway from Salvia miltiorrhiza. PLoS ONE 8(9):e73259. https://doi.org/10.1371/journal.pone.0073259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yang N, Zhou W, Su J, Wang X, Li L, Wang L, Cao X, Wang Z (2017) Overexpression of smMYC2 increases the production of phenolic acids in Salvia miltiorrhiza. Front Plant Sci 8(1804). https://doi.org/10.3389/fpls.2017.01804

  33. Petersen M, Simmonds MSJ (2003) Rosmarinic acid. Phytochemistry 62(2):121–125. https://doi.org/10.1016/S0031-9422(02)00513-7

    Article  CAS  PubMed  Google Scholar 

  34. Ma X-H, Ma Y, Tang J-F, He Y-L, Liu Y-C, Ma X-J, Shen Y, Cui G-H, Lin H-X, Rong Q-X, Guo J, Huang L-Q (2015) The biosynthetic pathways of tanshinones and phenolic acids in Salvia miltiorrhiza. Molecules 20(9):16235

    Article  CAS  PubMed  Google Scholar 

  35. Zhou Y, Sun W, Chen J, Tan H, Xiao Y, Li Q, Ji Q, Gao S, Chen L, Chen S, Zhang L, Chen W (2016) SmMYC2a and SmMYC2b played similar but irreplaceable roles in regulating the biosynthesis of tanshinones and phenolic acids in Salvia miltiorrhiza. Sci Rep 6:22852. https://doi.org/10.1038/srep22852

  36. Zhang S, Yan Y, Wang B, Liang Z, Liu Y, Liu F, Qi Z (2014) Selective responses of enzymes in the two parallel pathways of rosmarinic acid biosynthetic pathway to elicitors in Salvia miltiorrhiza hairy root cultures. J Biosci Bioeng 117(5):645–651. https://doi.org/10.1016/j.jbiosc.2013.10.013

    Article  CAS  PubMed  Google Scholar 

  37. Song Z, Li X (2015) Expression profiles of rosmarinic acid biosynthesis genes in two Salvia miltiorrhiza lines with differing water-soluble phenolic contents. Ind Crops Prod 71(Supplement C):24–30. doi:https://doi.org/10.1016/j.indcrop.2015.03.081

  38. Zhang S, Li H, Liang X, Yan Y, Xia P, Jia Y, Liang Z (2015) Enhanced production of phenolic acids in Salvia miltiorrhiza hairy root cultures by combing the RNAi-mediated silencing of chalcone synthase gene with salicylic acid treatment. Biochem Eng J 103(Supplement C):185–192. https://doi.org/10.1016/j.bej.2015.07.019

  39. Zhang Y, Yan Y-P, Wu Y-C, Hua W-P, Chen C, Ge Q, Wang Z-Z (2014) Pathway engineering for phenolic acid accumulations in Salvia miltiorrhiza by combinational genetic manipulation. Metab Eng 21(Supplement C):71–80. https://doi.org/10.1016/j.ymben.2013.10.009

  40. Ma Y, Yuan L, Wu B, Xe Li, Chen S, Lu S (2012) Genome-wide identification and characterization of novel genes involved in terpenoid biosynthesis in Salvia miltiorrhiza. J Exp Bot 63(7):2809–2823. https://doi.org/10.1093/jxb/err466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Arendt P, Pollier J, Callewaert N, Goossens A (2016) Synthetic biology for production of natural and new-to-nature terpenoids in photosynthetic organisms. Plant J 87(1):16–37. https://doi.org/10.1111/tpj.13138

    Article  CAS  PubMed  Google Scholar 

  42. Trikka FA, Nikolaidis A, Ignea C, Tsaballa A, Tziveleka L-A, Ioannou E, Roussis V, Stea EA, Božić D, Argiriou A, Kanellis AK, Kampranis SC, Makris AM (2015) Combined metabolome and transcriptome profiling provides new insights into diterpene biosynthesis in S. pomifera glandular trichomes. BMC Genom 16:935. https://doi.org/10.1186/s12864-015-2147-3

    Article  Google Scholar 

  43. Hao G, Shi R, Tao R, Fang Q, Jiang X, Ji H, Feng L, Huang L (2013) Cloning, molecular characterization and functional analysis of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (HDR) gene for diterpenoid tanshinone biosynthesis in Salvia miltiorrhiza Bge. f. alba. Plant Physiol Biochem 70(Supplement C):21–32. https://doi.org/10.1016/j.plaphy.2013.05.010

  44. Dai Z, Cui G, Zhou S-F, Zhang X, Huang L (2011) Cloning and characterization of a novel 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Salvia miltiorrhiza involved in diterpenoid tanshinone accumulation. J Plant Physiol 168(2):148–157. https://doi.org/10.1016/j.jplph.2010.06.008

    Article  CAS  PubMed  Google Scholar 

  45. Božić D, Papaefthimiou D, Brückner K, de Vos RCH, Tsoleridis CA, Katsarou D, Papanikolaou A, Pateraki I, Chatzopoulou FM, Dimitriadou E, Kostas S, Manzano D, Scheler U, Ferrer A, Tissier A, Makris AM, Kampranis SC, Kanellis AK (2015) Towards elucidating carnosic acid biosynthesis in lamiaceae: functional characterization of the three first steps of the pathway in Salvia fruticosa and Rosmarinus officinalis. PLoS ONE 10(5):e0124106. https://doi.org/10.1371/journal.pone.0124106

    Article  PubMed  PubMed Central  Google Scholar 

  46. Bai Z, Xia P, Wang R, Jiao J, Ru M, Liu J, Liang Z (2017) Molecular cloning and characterization of five SmGRAS genes associated with tanshinone biosynthesis in Salvia miltiorrhiza hairy roots. PLoS ONE 12(9):e0185322. https://doi.org/10.1371/journal.pone.0185322

    Article  PubMed  PubMed Central  Google Scholar 

  47. Zhang X, Luo H, Xu Z, Zhu Y, Ji A, Song J, Chen S (2015) Genome-wide characterisation and analysis of bHLH transcription factors related to tanshinone biosynthesis in Salvia miltiorrhiza. Sci Rep 5:11244. https://doi.org/10.1038/srep11244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ma Y, Ma X-H, Meng F-Y, Zhan Z-L, Guo J, Huang L-Q (2016) RNA interference targeting CYP76AH1 in hairy roots of Salvia miltiorrhiza reveals its key role in the biosynthetic pathway of tanshinones. Biochem Biophys Res Commun 477(2):155–160. https://doi.org/10.1016/j.bbrc.2016.06.036

    Article  CAS  PubMed  Google Scholar 

  49. Kai G, Xu H, Zhou C, Liao P, Xiao J, Luo X, You L, Zhang L (2011) Metabolic engineering tanshinone biosynthetic pathway in Salvia miltiorrhiza hairy root cultures. Metab Eng 13(3):319–327. https://doi.org/10.1016/j.ymben.2011.02.003

    Article  CAS  PubMed  Google Scholar 

  50. Yadav VG, De Mey M, Giaw Lim C, Kumaran Ajikumar P, Stephanopoulos G (2012) The future of metabolic engineering and synthetic biology: Towards a systematic practice. Metab Eng 14(3):233–241. https://doi.org/10.1016/j.ymben.2012.02.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sun H, Liu Z, Zhao H, Ang EL (2015) Recent advances in combinatorial biosynthesis for drug discovery. Drug Des Dev Ther 9:823–833. https://doi.org/10.2147/dddt.s63023

    Google Scholar 

  52. Kampranis SC, Makris AM (2012) Developing a yeast cell factory for the production of terpenoids. Comput Struct Biotechnol J 3:e201210006. https://doi.org/10.5936/csbj.201210006

    Article  PubMed  PubMed Central  Google Scholar 

  53. Zebec Z, Wilkes J, Jervis AJ, Scrutton NS, Takano E, Breitling R (2016) Towards synthesis of monoterpenes and derivatives using synthetic biology. Curr Opin Chem Biol 34(Supplement C):37–43. https://doi.org/10.1016/j.cbpa.2016.06.002

  54. Zhang H, Liu Q, Cao Y, Feng X, Zheng Y, Zou H, Liu H, Yang J, Xian M (2014) Microbial production of sabinene—a new terpene-based precursor of advanced biofuel. Microb Cell Fact 13(1):20. https://doi.org/10.1186/1475-2859-13-20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ignea C, Pontini M, Maffei ME, Makris AM, Kampranis SC (2014) Engineering monoterpene production in yeast using a synthetic dominant negative geranyl diphosphate synthase. ACS Synth Biol 3(5):298–306. https://doi.org/10.1021/sb400115e

    Article  CAS  PubMed  Google Scholar 

  56. Ignea C, Cvetkovic I, Loupassaki S, Kefalas P, Johnson CB, Kampranis SC, Makris AM (2011) Improving yeast strains using recyclable integration cassettes, for the production of plant terpenoids. Microb Cell Fact 10(1):4. https://doi.org/10.1186/1475-2859-10-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ignea C, Athanasakoglou A, Ioannou E, Georgantea P, Trikka FA, Loupassaki S, Roussis V, Makris AM, Kampranis SC (2016) Carnosic acid biosynthesis elucidated by a synthetic biology platform. Proc Natl Acad Sci 113(13):3681–3686. https://doi.org/10.1073/pnas.1523787113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ignea C, Athanasakoglou A, Andreadelli A, Apostolaki M, Iakovides M, Stephanou EG, Makris AM, Kampranis SC (2017) Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast. Sci Rep 7(1):8855. https://doi.org/10.1038/s41598-017-09592-5

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vasil Georgiev .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Georgiev, V., Pavlov, A. (2017). Genetic Engineering and Manipulation of Metabolite Pathways in Salvia Spp.. In: Georgiev, V., Pavlov, A. (eds) Salvia Biotechnology. Springer, Cham. https://doi.org/10.1007/978-3-319-73900-7_10

Download citation

Publish with us

Policies and ethics