Papaver somniferum L. taxonomy, uses and new insight in poppy alkaloid pathways

Abstract

Since ancient times, opium poppy (Papaver somniferum L.) is known for its medicinal properties, related to its secondary metabolite content. Its most important secondary metabolites, called benzylisoquinoline alkaloids (BIAs), are still essential in pharmaceutical field. Few of them, like morphine, have specific clinical application but also effects on CNS. Not all poppy cultivars are able to biosynthesize morphine in high amount, making this plant useful for other purposes like food uses. For this reason it is crucial to deeply understand the origin of poppy, its possible use and have a deep knowledge of the BIA biosynthesis. These aspects are crucial for the final use of P. somniferum. This review aims to summarize the state-of-the-art on its taxonomy and origin beside its uses and BIA biosynthetic pathways, its most important metabolites. The review focuses on conflicting or unsolved questions about enzymatic localization, role of different plant organs in the biosynthesis, and storage and external conditions that influence the alkaloid production, highlighting the significant involvement of transcription factors. Behind this review, there is the firm belief that only a deep knowledge of alkaloid biosynthetic processes could lead to the characterization of undefined step and to the development of engineering cultivars optimizing the potential uses of P. somniferum. The goal is answer in more sustainable way to ever-increasing worldwide request of such products, in particular morphine and derivates, obtaining high morphine content cultivars useful for pharmaceutical market or no morphine producing cultivars appreciated as food. Devising cultivars with different BIA content could lead to decrease, or even avoid, illicit use and illegal extraction, confining only low alkaloid content cultivars to consumers market.

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Abbreviations

3′OHase:

3′-Hydroxylase

3′OMT:

3′-O-methyltransferase

3OHase:

Tyrosine/tyramine 3-hydroxylase

4′OMT:

3′-hydroxyl-N-methylcoclaurine 4′-O-methyltransferase

4HPAA:

4 Hydroxyphenylacetic acid

4HPPDC:

4-Hydroxyphenylpuruvate decarboxylase

6OMT:

Norcoclaurine 6-O-methyltransferase

7OMT:

Reticuline 7-O-methyltransferase

AC:

Adenylyl cyclase

AFLP:

Amplified fragment length polymorphism

AMP:

Adenosine monophosphate

AMPc:

Adenosine monophosphate cyclic

BBE:

Berberine bridge enzyme

BIAs:

Benzylisoquinoline alkaloids

CAS:

Canadine synthase

CFS:

Cheilanthifoline synthase

CNMT:

Coclaurine N-methyltransferase

CNS:

Central nervous system

CODM:

Codeine O-demethylase

CoOMT:

Columbamine O-methyltransferase

COR:

Codeinone reductase

CPVO:

Community Plant Variety Office

CYP:

Cytochrome P450 enzyme family

CYP82Y1:

N-methylcanadine 1-hydroxylase

CYP80B:

(S)-N-methylcoclaurine 3′-hydroxylase isozyme

Cys:

Cysteine

DA:

Dopamine

DBOX:

Dihydrosanguinarine oxidase

EFSA:

European Food Safety Authority

ER:

Endoplasmic reticulum

EST:

Expressed sequence tag

FT–ICR–MS:

Fourier-transform–ion-cyclotron resonance–mass spectrometry

GC:

Gas chromatography

GPCR:

G protein–coupled receptors

HPLC:

High performance liquid chromatography

MeJa:

Methyl jasmonate

MIA:

Monoterpenoid indole alkaloid

MLP15:

Major latex proteins

MSH:

N-methylstylopine 14-hydroxylase

N7OMT:

Norreticuline 7-O-methyltransferase

NAc:

Nucleus accumbens

NCS:

Norcoclaurine synthase

NMCH:

N-methylcoclaurine 3′-hydroxylase

NOS:

Noscapine synthase

Nuclear factor-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

OR receptors:

Receptors for endogenous opiates

ORL1:

Opioid receptor-like

P6H:

Protopine 6-hydroxylase

PKA:

Protein kinase A

PKC:

Protein kinase C

PPH:

Protopine-6-hydroxylase

RAPD:

Random amplified polymorphic DNA

RFLP:

Restriction fragment length polymorphism

ROS:

Reactive oxygen species

RSP:

Restriction site polymorphism

RVM:

Rostral ventromedial medulla

SalAT:

Salutaridinol 7-O-acetyltransferase

SalR:

Salutaridine reductase

SanR:

Sanguinarine reductase

SAT:

(7S)-salutaridinol 7-O-acetyltransferase

SNPs:

Single nucleotide polymorphism

SOMT1:

Scoulerine 9-O-methyltransferase

SOR:

7-Oxidoreductase

SPS:

Stylopine synthase

STOX:

(S)-tetrahydroxyprotoberberineoxidase

STRs:

Short tandem repeat

STS:

Salutaridine synthase

StySyn:

Sstylopine synthase

T6ODM:

Thebaine 6-O-demethylase

TFBSs:

Transcription factor binding bites

TFs:

Transcription factors

TNMT:

Tetrahydroprotoberberine N-methyltransferase

TYDC:

Tyrosine/DOPA decarboxylase

UHPLC–ESI–QTOF–MS:

Ultra high performance liquid chromatography–electrospray ionization–quadrupole time-of-flight–mass spectrometry

VNTRs:

Variable number of tandem repeat or minisatellites

References

  1. Acheson RM, Harper JL, Mcnaughton IH (1956) Distribution of anthocyanin pigments in poppies. Nature 178:1283–1284

    Article  CAS  Google Scholar 

  2. Acheson RM, Jenkins CL, Harper JL et al (2006) Floral pigments in papaver and their significance in the systematics of the genus. New Phytol 61(3):256–260

    Article  Google Scholar 

  3. Agarwal PS, Lakhwani D et al (2016) Comparative analysis of transcription factor gene families from Papaver somniferum: identification of regulatory factors involved in benzylisoquinoline alkaloid biosynthesis. Protoplasma 253(3):857–871

    Article  PubMed  CAS  Google Scholar 

  4. Bajpai S, Gupta AP, Gupta MM et al (2000) Inter-relation between descriptors and morphine yield in Asian germplasm of opium poppy Papaver somniferum. Genet Resour Crop Evol 47(3):315–322

    Article  Google Scholar 

  5. Batterham RL, Cowley MA, Small CJ et al (2004) Physiology: does gut hormone PYY3-36 decrease food intake in rodents? Nature 430(6996):413–414

    Google Scholar 

  6. Beaudoin GA, Facchini JP (2014) Benzylisoquinoline alkaloid biosynthesis in opium poppy. Planta 240(1):19–32

    Article  PubMed  CAS  Google Scholar 

  7. Bird DA, Franceschi VR, Facchini PJ (2003) A tale of three cell types: alkaloid biosynthesis is localized to sieve elements in opium poppy. The Plant Cell 15:2626–2635

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Celik I, Gultekin V, Allmer J et al (2014) Development of genomic simple sequence repeat markers in opium poppy by next-generation sequencing. Mol Breed 34(2):323–334

    Article  CAS  Google Scholar 

  9. Danert S (1958) Zur Systematik von Papaver somniferum L. Kulturpflanze 6:61–88

    Article  Google Scholar 

  10. Dang TT, Onoyovwi A, Farrow SC et al (2012) Biochemical genomics for gene discovery in benzylisoquinoline alkaloid biosynthesis in opium poppy and related species. Methods Enzymol 515:231–266

    Article  PubMed  CAS  Google Scholar 

  11. Darokar MP, Dhawan SS, Shukla AK et al (2014) Assessment of genetic relatedness among selected cultivars of opium poppy (Papaver somniferum L.) through DNA profiling. Acta Hortic 1036:21–28

    Article  Google Scholar 

  12. Desgagné-Penix I, Khan MF, Schremier DC et al (2010) Integration of deep transcriptome and proteome analyses reveals the components of alkaloid metabolism in opium poppy cell cultures. BMC Plant Biol 10(1):252

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Desgagné-Penix I, Farrow SC, Cram D et al (2012) Integration of deep transcript and targeted metabolite profiles for eight cultivars of opium poppy. Plant Mol Biol 79(3):295–313

    Article  PubMed  CAS  Google Scholar 

  14. Dittbrenner A, Lohwasser U, Mock HP et al (2008) Molecular and phytochemical studies of Papaver somniferum in the context of infraspecific classification. Acta Hortic 799:81–88

    Article  CAS  Google Scholar 

  15. Duarte DF (2005) Uma breve história do ópio e dos opióides. Rev Bras Anestesiol 55(1):135–146

    PubMed  Google Scholar 

  16. Egan PA, Pendry CA, Shresth S (2011) Flora of Nepal Papaveraceae. Royal Botanic Gardens, Melbourne

    Google Scholar 

  17. El Nehir S, Karakaya S (2004) Radical scavenging and iron-chelating activities of some greens used as traditional dishes in mediterranean diet. Int J Food Sci Nutr 55(1):67–74

    Article  CAS  Google Scholar 

  18. Eryilmaz T, Yesilyurt MK, Cesur C et al (2016) Biodiesel production potential from oil seeds in Turkey. Renew Sustain Energy Rev 58:842–851

    Article  CAS  Google Scholar 

  19. European Food Safety Authority (EFSA) (2011) Scientific opinion on the risks for public health related to the presence of opium alkaloids in poppy seeds. EFSA J 9(11):1–150

    Google Scholar 

  20. Facchini PJ (2001) Alkaloid biosynthesis in plants: biochemistry, cell biology, molecular regulation, and metabolic engineering applications. Annu Rev Plant Biol 52(1):29–66

    Article  CAS  Google Scholar 

  21. Facchini PJ, De Luca V (2008) Opium poppy and Madagascar periwinkle: model non-model systems to investigate alkaloid biosynthesis in plants. Plant Journal 54(4):763–784

    Article  PubMed  CAS  Google Scholar 

  22. Fernández EC, Rajchl A, Lachman J et al (2013) Impact of yacon landraces cultivated in the Czech Republic and their ploidy on the short- and long-chain fructooligosaccharides content in tuberous roots. LWT Food Sci Technol 54(1):80–86

    Article  CAS  Google Scholar 

  23. Froede R (1972) Drugs of abuse: legal and illegal. Hum Pathol 3(1):23–36

    Article  PubMed  CAS  Google Scholar 

  24. Gurkok T, Turktas M, Parmaksiz I et al (2015) Transcriptome profiling of alkaloid biosynthesis in elicitor induced opium poppy. Plant Mol Biol Rep 33(3):673–688

    Article  CAS  Google Scholar 

  25. Hagel JM, Facchini PJ (2013) Benzylisoquinoline alkaloid metabolism: a century of discovery and a brave new world. Plant Cell Physiol 54(5):647–672

    Article  PubMed  CAS  Google Scholar 

  26. Hammer K (1981) Problems of Papaver somniferum classification and some remarks on recently collected European poppy land-races. Genet Resour Crop Evol 29:287–296

    Google Scholar 

  27. Hao D, Xiao JG, Pei GX (2015) Medicinal plant: chemistry, biology and omics. Woodhead Publishing, Cambridge

    Google Scholar 

  28. Hofman PJ, Menary RC (1985) Alkaloid losses from the capsules of Papaver Somniferum L. during kiln drying and storage under commercial conditions in Tasmania. J Stored Prod Res 21(3):135–139

    Article  CAS  Google Scholar 

  29. Inukai S, Hong Kock K, Bulyk ML (2017) Transcription factor-DNA binding: beyond binding site motifs. Curr Opin Genet Dev 43:110–119. https://doi.org/10.1016/j.gde.2017.02.007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Jablonická V, Mansfeld J, Heilmann I et al (2016) Identification of a secretory phospholipase A2 from Papaver somniferum L. that transforms membrane phospholipids. Phytochemistry 129:4–13

    Article  PubMed  CAS  Google Scholar 

  31. Jia L, Clegg MT, Jiang T (2004) Evolutionary dynamics of the DNA-binding domains in putative R2R3-MYB genes identified from rice subspecies indica and japonica genomes. Plant Physiol 134(2):575–585

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Kadereit JW (1988) Sectional affinities and geographical distribution in the genus Papaver L. (Papaveraceae). Beitrage zur Biologie der Pflanzen 63:139–156

    Google Scholar 

  33. Kakeshpour T, Nayebi S, Rashidi Monfared S et al (2015) Identification and expression analyses of MYB and WRKY transcription factor genes in Papaver somniferum L. Physiol Mol Biol Plants 21(4):465–478

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Kreek MJ (2007) Opioids, dopamine, stress, and the addictions. Dialog Clin Neurosci 9(4):363–378

    Google Scholar 

  35. Kutchan TM, Weid M, Ziegler J (2004) The roles of latex and the vascular bundle in morphine biosynthesis in the opium poppy, Papaver somniferum. Proc Natl Acad Sci USA 101(38):13957–13962

    Article  PubMed  Google Scholar 

  36. Li Q, Zhang H (2017) Research progress on the synthesis of morphine alkaloids. Chin J Organ Chem 37(7):1629–1652

    Article  CAS  Google Scholar 

  37. Liscombe DK, Facchini PJ (2008) Evolutionary and cellular webs in benzylisoquinoline alkaloid biosynthesis. Curr Opin Biotechnol 19(2):173–180

    Article  PubMed  CAS  Google Scholar 

  38. Marciano MA, Panicker SX et al (2018) Development of a method to extract opium poppy (Papaver somniferum L.) DNA from heroin. Sci Rep 8:2590. https://doi.org/10.1038/s41598-018-20996-9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Meos A, Saks L, Raal A (2017) Content of alkaloids in ornamental Papaver somniferum L. cultivars growing in estonia. Proc Est Acad Sci 66(1):34–39

    Article  Google Scholar 

  40. Mishra S, Triptahi V, Singh S, Phukan UJ, Gupta MM, Shanker K, Shukla RK (2013) Wound induced tanscriptional regulation of benzylisoquinoline pathway and characterization of wound inducible PsWRKY transcription factor from Papaver somniferum. PLoS ONE 8(1):e52784. https://doi.org/10.1371/journal.pone.0052784

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Mitrová K, Svoboda P, Milella L et al (2018) Alliinase and cysteine synthase transcription in developing garlic (Allium sativum L.) over time. Food Chem 15(251):103–109. https://doi.org/10.1016/j.foodchem.2017.12.090

    Article  CAS  Google Scholar 

  42. Moloney MG (2016) Natural products as a source for novel antibiotics. Trends Pharmacol Sci 37(8):689–701

    Article  PubMed  CAS  Google Scholar 

  43. Onoyovwe A, Hagel JM, Chen X et al (2013) Morphine biosynthesis in opium poppy involves two cell types: sieve elements and laticifers. Plant Cell 25(10):4110–4122

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Ovesná J, Kučera L, Vaculová K et al (2013) Analysis of the genetic structure of a barley collection using DNA diversity array technology (DArT). Plant Mol Bio Rep 31(2):280–288

    Article  CAS  Google Scholar 

  45. Pathak S, Lakhwani D, Gupta P et al (2013) Comparative transcriptome analysis using high papaverine mutant of Papaver Somniferum reveals pathway and uncharacterized steps of papaverine biosynthesis. PLoS ONE 8(5):e65622. https://doi.org/10.1371/journal.pone.0065622

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Prajapati S, Bajpai S, Singh D et al (2002) Alkaloid profiles of the Indian land races of the opium poppy Papaver somniferum L. Genet Resour Crop Evol 49(2):183–188

    Article  Google Scholar 

  47. Prescha A, Grajzer M, Dedyk M et al (2014) The Antioxidant activity and oxidative stability of cold-pressed oils. J Am Oil Chem Soc 91(8):1291–1301

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Russo D, Valentão P, Andrade PB et al (2015) Evaluation of antioxidant, antidiabetic and anticholinesterase activities of Smallanthus sonchifolius landraces and correlation with their phytochemical profiles. Int J Mol Sci 16(8):17696–17718

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Saunders JM, Pedroni MJ, Penrose LDJ et al (2000) AFLP analysis of opium poppy. Crop Sci 41(5):1596–1601

    Article  Google Scholar 

  50. Şelale H, Çelik I, Visam Gü V et al (2013) Development of EST-SSR markers for diversity and breeding studies in opium poppy. Plant Breed 132(3):344–351

    Article  CAS  Google Scholar 

  51. Singh M, Chaturvedi N, Shasany AK et al (2014) Impact of promising genotypes of Papaver somniferum L. developed for beneficial uses. Acta Hortic 1036:29–41

    Article  Google Scholar 

  52. Sofo A, Milella L, Tataranni G (2010) Effects of Trichoderma harzianum strain T-22 on the growth of two Prunus rootstocks during the rooting phase. J Hortic Sci Biotechnol 85(6):497–502

    Article  Google Scholar 

  53. Solanki G, Dodiya NS, Kunwar R et al (2017) Character Association and path coefficient analysis for seed yield and latex yield in opium poppy (Papaver somniferum L.). Int J Cur Microbiol Appl Sci 6(8):1116–1123

    Article  Google Scholar 

  54. Stefano GB, Pilonis N, Ptacek R et al (2017) Reciprocal evolution of opiate science from medical and cultural perspectives. Med Sci Monit 23:2890–2896

    Article  PubMed  PubMed Central  Google Scholar 

  55. Tavakkoli Z, Assadi M (2016) Evaluation of seed and leaf epidermis characters in the taxonomy of some annual species of the genus papaver (Papaveraceae). Nord J Bot 34(3):302–321

    Article  Google Scholar 

  56. Tétényi P (1997) Opium botany and horticulture. In: Janick J (ed) Horticultural reviews, vol 19. Wiley, New York, pp 375–382

    Google Scholar 

  57. Wang H, Wang H, Shao H et al (2016) Recent advances in utilizing transcription factors to improve plant abiotic stress tolerance by transgenic technology. Front Plant Sci 7:1–13

    PubMed  PubMed Central  Google Scholar 

  58. Winzer T, Gazda V, Zhesi H et al (2012) A papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine. Science 336(6089):1704–1708

    Article  PubMed  CAS  Google Scholar 

  59. Ziegler J, Facchini PJ, Rene G et al (2009) Evolution of morphine biosynthesis in opium poppy. Phytochemistry 70(15–16):1696–1707

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Authors would like to thank the Czech Minstry of Agriculture, Projects NAZV QK1720263 and RO0417 for the support.

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Correspondence to Luigi Milella.

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Labanca, F., Ovesnà, J. & Milella, L. Papaver somniferum L. taxonomy, uses and new insight in poppy alkaloid pathways. Phytochem Rev 17, 853–871 (2018). https://doi.org/10.1007/s11101-018-9563-3

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Keywords

  • Benzylisoquinoline alkaloid
  • BIAs
  • Biosynthesis
  • Poppy
  • Phylogenetic
  • Transcription factors