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Triterpene Functional Genomics in Ocimum

  • Sumit Ghosh
Chapter
Part of the Compendium of Plant Genomes book series (CPG)

Abstract

Triterpenes, isoprene-derived 30-carbon compounds, constitute a large class of natural products with enormous structural and functional diversity. Bioactive triterpenes are used as ingredients in pharmaceuticals, foods, and cosmetics. Ocimum species are known to produce bioactive triterpenes such as ursolic acid, oleanolic acid, betulinic acid, alphitolic acid, euscaphic acid, and epi-maslinic acid. Functional genomics studies conducted in O. basilicum led to identification and characterization of oxidosqualene cyclases (OSCs) and cytochrome P450s (P450s) for the biosynthesis of ursolic acid and oleanolic acid, and opened up the prospects for producing bioactive triterpenes in alternate microbial hosts such as yeast. Moreover, a recent advancement in the area of high-throughput sequencing of genomes and transcriptomes provided an opportunity to understand the molecular and biochemical basis for the biosynthesis of diverse triterpenes and other phytochemicals in Ocimum species.

Keywords

Phytochemical Triterpene Oxidosqualene cyclase P450 VIGS RNAi Transgenics 

References

  1. Abe I (2014) The oxidosqualene cyclases: one substrate, diverse products. In: Osbourn A, Goss RJ, Carter GT (eds) Natural products: discourse, diversity, and design. Wiley, Hoboken, NJ, USA, pp 293–316CrossRefGoogle Scholar
  2. Arendt P, Miettinen K, Pollier J, De Rycke R, Callewaert N, Goossens A (2017) An endoplasmic reticulum-engineered yeast platform for overproduction of triterpenoids. Metab Eng 40:165–175CrossRefGoogle Scholar
  3. Bai LY, Chiu CF, Chiu SJ, Chen YW, Hu JL, Wu CY, Weng JR (2015) Alphitolic acid, an anti-inflammatory triterpene, induces apoptosis and autophagy in oral squamous cell carcinoma cells, in part, through a p53-dependent pathway. J Funct Foods 18:368–378CrossRefGoogle Scholar
  4. Banerjee S, Singh S, Ur Rahman L (2012) Biotransformation studies using hairy root cultures - a review. Biotechnol Adv 30:461–468CrossRefGoogle Scholar
  5. Biazzi E, Carelli M, Tava A, Abbruscato P, Losini I, Avato P, Scotti C, Calderini O (2015) CYP72A67 catalyzes a key oxidative step in Medicago truncatula haemolytic saponin biosynthesis. Mol Plant 8:1493–1506CrossRefGoogle Scholar
  6. Carelli M, Biazzi E, Panara F, Tava A, Scaramelli L, Porceddu A, Graham N, Odoardi M, Piano E, Arcioni S, May S, Scotti C, Calderini O (2011) Medicago truncatula CYP716A12 is a multifunctional oxidase involved in the biosynthesis of hemolytic saponins. Plant Cell 23:3070–3081CrossRefGoogle Scholar
  7. Datta A, Ghosh S (2015) Agricultural biotechnology for food sufficiency and benefit to human health (Chap. 72). In: Talwar GP, Hasnain SE, Sarin SK (eds) Textbook of biochemistry, biotechnology, allied & molecular medicine, under section VIII, human genetics, biochemical basis of inheritance, expression of genetic information, genetic engineering. Prentics Hall, India, pp 877–896Google Scholar
  8. Delis C, Krokida A, Georgiou S, Pena-Rodriguez LM, Kavroulakis N, Ioannou E, Roussis V, Osbourn AE, Papadopoulou KK (2011) Role of lupeol synthase in Lotus japonicus nodule formation. New Phytol 189:335–346CrossRefGoogle Scholar
  9. Deschamps C, Simon JE (2002) Agrobacterium tumefaciens-mediated transformation of Ocimum basilicum and O. citriodorum. Plant Cell Rep 21:359–364CrossRefGoogle Scholar
  10. Fellmann C, Lowe SW (2014) Stable RNA interference rules for silencing. Nat Cell Biol 16(1):10–18CrossRefGoogle Scholar
  11. Gang DR, Wang J, Dudareva N, Nam KH, Simon JE, Lewinsohn E, Pichersky E (2001) An investigation of the storage and biosynthesis of phenylpropenes in sweet basil. Plant Physiol 125:539–555CrossRefGoogle Scholar
  12. Gelvin SB (2003) Agrobacterium-mediated plant transformation: the biology behind the “gene-jockeying” tool. Microbiol Mol Biol Rev 67:16–37CrossRefGoogle Scholar
  13. Ghosh S (2016) Biosynthesis of structurally diverse triterpenes in plants: the role of oxidosqualene cyclases. Proc Indian Nat Sci Acad 82:1189–1210CrossRefGoogle Scholar
  14. Ghosh S (2017) Triterpene structural diversification by plant cytochrome P450 enzymes. Front Plant Sci 8:1886CrossRefGoogle Scholar
  15. Go YS, Lee SB, Kim HJ, Kim J, Park HY, Kim JK (2012) Identification of marneral synthase, which is critical for growth and development in Arabidopsis. Plant J 72:791–804CrossRefGoogle Scholar
  16. Hill RA, Connolly JD (2013) Triterpenoids. Nat Prod Rep 30:1028–1065CrossRefGoogle Scholar
  17. Hill RA, Connolly JD (2017) Triterpenoids. Nat Prod Rep 34:90–122CrossRefGoogle Scholar
  18. Jager S, Trojan H, Kopp T, Laszczyk MN, Scheffler A (2009) Pentacyclic triterpene distribution in various plants-rich sources for a new group of multipotent plant extracts. Molecules 14:2016–2031CrossRefGoogle Scholar
  19. Jayaramaiah RH, Anand A, Beedkar SD, Dholakia BB, Punekar SA, Kalunke RM, Gade WN, Thulasiram HV, Giri AP (2016) Functional characterization and transient expression manipulation of a new sesquiterpene synthase involved in β-caryophyllene accumulation in Ocimum. Biochem Biophys Res Commun 473:265–271CrossRefGoogle Scholar
  20. Kapteyn J, Qualley AV, Xie Z, Fridman E, Dudareva N, Gang DR (2007) Evolution of cinnamate/p-coumarate carboxyl methyltransferases and their role in the biosynthesis of methylcinnamate. Plant Cell 19:3212–3229CrossRefGoogle Scholar
  21. Kemen AC, Honkanen S, Melton RE, Findlay KC, Mugford ST, Hayashi K, Haralampidis K, Rosser SJ, Osbourn A (2014) Investigation of triterpene synthesis and regulation in oats reveals a role for β-amyrin in determining root epidermal cell patterning. Proc Natl Acad Sci USA 111:8679–8684CrossRefGoogle Scholar
  22. Khan S, Fahim N, Singh P, Rahman LU (2015) Agrobacterium tumefaciens mediated genetic transformation of Ocimum gratissimum: a medicinally important crop. Indust Crops Prod 71:138–146CrossRefGoogle Scholar
  23. Kushiro T, Shibuya M, Masuda K, Ebizuka Y (2000) Mutational studies on triterpene synthases: engineering lupeol synthase into β-amyrin synthase. J Am Chem Soc 122:6816–6824CrossRefGoogle Scholar
  24. Lee LY, Gelvin SB (2008) T-DNA binary vectors and systems. Plant Physiol 146:325–332CrossRefGoogle Scholar
  25. Lee SY, Kim HH, Park SU (2015) Recent studies on betulinic acid and its biological and pharmacological activity. EXCLI J 14:199–203PubMedPubMedCentralGoogle Scholar
  26. Li YC, Tian K, Sun LJ, Long H, Li LJ, Wu ZZ (2016) A new hexacyclic triterpene acid from the roots of Euscaphis japonica and its inhibitory activity on triglyceride accumulation. Fitoterapia 109:261–265CrossRefGoogle Scholar
  27. Liang CQ, Shi YM, Li XY, Luo RH, Li Y, Zheng YT, Zhang HB, Xiao WL, Sun HD (2013) Kadcotriones AC: tricyclic triterpenoids from Kadsura coccinea. J Nat Prod 76:2350–2354CrossRefGoogle Scholar
  28. Liu Y, Schiff M, Marathe R, Dinesh-Kumar SP (2002) Tobacco Rar1, EDS1 and NPR1/NIM1 like genes are required for N-mediated resistance to tobacco mosaic virus. Plant J 30:415–429CrossRefGoogle Scholar
  29. Loman NJ, Misra RV, Dallman TJ, Constantinidou C, Gharbia SE, Wain J, Pallen MJ (2012) Performance comparison of benchtop high-throughput sequencing platforms. Nat Biotechnol 30:434–439CrossRefGoogle Scholar
  30. Lu R, Martin-Hernandez AM, Peart JR, Malcuit I, Baulcombe DC (2003) Virus-induced gene silencing in plants. Methods 30:296–303CrossRefGoogle Scholar
  31. Marzouk AM (2009) Hepatoprotective triterpenes from hairy root cultures of Ocimum basilicum L. Z Naturforsch C 64:201–209CrossRefGoogle Scholar
  32. Meng FY, Sun JX, Li X, Yu HY, Li SM, Ruan HL (2011) Schiglautone A, a new tricyclic triterpenoid with a unique 6/7/9-fused skeleton from the stems of Schisandra glaucescens. Org Lett 13:1502–1505CrossRefGoogle Scholar
  33. Misra RC, Maiti P, Chanotiya CS, Shanker K, Ghosh S (2014) Methyl jasmonate-elicited transcriptional responses and pentacyclic triterpene biosynthesis in sweet basil. Plant Physiol 164:1028–1044CrossRefGoogle Scholar
  34. Misra RC, Sharma S, Sandeep Garg A, Chanotiya CS, Ghosh S (2017) Two CYP716A subfamily cytochrome P450 monooxygenases of sweet basil play similar but nonredundant roles in ursane- and oleanane-type pentacyclic triterpene biosynthesis. New Phytol 214:706–720CrossRefGoogle Scholar
  35. Moses T, Pollier J, Thevelein JM, Goossens A (2013) Bioengineering of plant (tri)terpenoids: from metabolic engineering of plants to synthetic biology in vivo and in vitro. New Phytol 200:27–43CrossRefGoogle Scholar
  36. Nicholas HJ (1961) Determination of sterol and triterpene content of Ocimum basilicum and Salvia officinalis at various stages of growth. J Pharm Sci 50:645–647CrossRefGoogle Scholar
  37. Osbourn A, Goss RJ, Field RA (2011) The saponins: polar isoprenoids with important and diverse biological activities. Nat Prod Rep 28:1261–1268CrossRefGoogle Scholar
  38. Pandey H, Pandey P, Singh S, Gupta R, Banerjee S (2015) Production of anti-cancer triterpene (betulinic acid) from callus cultures of different Ocimum species and its elicitation. Protoplasma 252:647–655CrossRefGoogle Scholar
  39. Papadopoulou K, Melton RE, Leggett M, Daniels MJ, Osbourn AE (1999) Compromised disease resistance in saponin-deficient plants. Proc Natl Acad Sci USA 96:12923–12928CrossRefGoogle Scholar
  40. Pu JX, Xiao WL, Lu Y, Li RT, Li HM, Zhang L, Huang SX, Li X, Zhao QS, Zheng QT, Sun HD (2005) Kadlongilactones A and B, two novel triterpene dilactones from Kadsura longipedunculata possessing a unique skeleton. Org Lett 7:5079–5082CrossRefGoogle Scholar
  41. Rastogi S, Kumar R, Chanotiya CS, Shanker K, Gupta MM, Nagegowda DA, Shasany AK (2013) 4-Coumarate: CoA ligase partitions metabolites for eugenol biosynthesis. Plant Cell Physiol 54:1238–1252CrossRefGoogle Scholar
  42. Rastogi S, Meena S, Bhattacharya A, Ghosh S, Shukla RK, Sangwan NS, Lal RK, Gupta MM, Lavania UC, Gupta V, Nagegowda DA, Shasany AK (2014) De novo sequencing and comparative analysis of holy and sweet basil transcriptomes. BMC Genom 15:588CrossRefGoogle Scholar
  43. Rastogi S, Kalra A, Gupta V, Khan F, Lal RK, Tripathi AK, Parameswaran S, Gopalakrishnan C, Ramaswamy G, Shasany AK (2015) Unravelling the genome of Holy basil: an “incomparable” “elixir of life” of traditional Indian medicine. BMC Genom 16:413CrossRefGoogle Scholar
  44. Reddy VA, Wang Q, Dhar N, Kumar N, Venkatesh PN, Rajan C, Panicker D, Sridhar V, Mao HZ, Sarojam R (2017) Spearmint R2R3-MYB transcription factor MsMYB negatively regulates monoterpene production and suppresses the expression of geranyl diphosphate synthase large subunit (MsGPPS.LSU). Plant Biotechnol J 15:1105–1119CrossRefGoogle Scholar
  45. Reed J, Stephenson MJ, Miettinen K, Brouwer B, Leveau A, Brett P, Goss RJM, Goossens A, O’Connell MA, Osbourn A (2017) A translational synthetic biology platform for rapid access to gram-scale quantities of novel drug-like molecules. Metab Eng 42:185–193CrossRefGoogle Scholar
  46. Robertson D (2004) VIGS vectors for gene silencing: many targets, many tools. Annu Rev Plant Biol 55:495–519CrossRefGoogle Scholar
  47. Ron M, Kajala K, Pauluzzi G, Wang D, Reynoso MA, Zumstein K, Garcha J, Winte S, Masson H, Inagaki S, Federici F, Sinha N, Deal RB, Bailey-Serres J, Brady SM (2014) Hairy root transformation using Agrobacterium rhizogenes as a tool for exploring cell type-specific gene expression and function using tomato as a model. Plant Physiol 166:455–469CrossRefGoogle Scholar
  48. Roy A, Saraf S (2006) Limonoids: overview of significant bioactive triterpenes distributed in plants kingdom. Biol Pharm Bull 29:191–201CrossRefGoogle Scholar
  49. Ruiz MT, Voinnet O, Baulcombe DC (1998) Initiation and maintenance of virus-induced gene silencing. Plant Cell 10:937–946CrossRefGoogle Scholar
  50. Sawai S, Saito K (2011) Triterpenoid biosynthesis and engineering in plants. Front Plant Sci 2:25CrossRefGoogle Scholar
  51. Shang Y, Ma Y, Zhou Y, Zhang H, Duan L, Chen H, Zeng J, Zhou Q, Wang S, Gu W, Liu M, Ren J, Gu X, Zhang S, Wang Y, Yasukawa K, Bouwmeester HJ, Qi X, Zhang Z, Lucas WJ, Huang S (2014) Biosynthesis, regulation, and domestication of bitterness in cucumber. Science 346:1084–1088CrossRefGoogle Scholar
  52. Sheng H, Sun H (2011) Synthesis, biology and clinical significance of pentacyclic triterpenes: a multi-target approach to prevention and treatment of metabolic and vascular diseases. Nat Prod Rep 28:543–593CrossRefGoogle Scholar
  53. Siddiqui BS, Aslam H, Ali ST, Begum S, Khatoon N (2007) Two new triterpenoids and a steroidal glycoside from the aerial parts of Ocimum basilicum. Chem Pharm Bull (Tokyo) 55:516–519CrossRefGoogle Scholar
  54. Silva MG, Vieira IG, Mendes FN, Albuquerque IL, dos Santos RN, Silva FO, Morais SM (2008) Variation of ursolic acid content in eight Ocimum species from northeastern Brazil. Molecules 13:2482–2487CrossRefGoogle Scholar
  55. Sohrabi R, Huh JH, Badieyan S, Rakotondraibe LH, Kliebenstein DJ, Sobrado P, Tholl D (2015) In planta variation of volatile biosynthesis: an alternative biosynthetic route to the formation of the pathogen-induced volatile homoterpene DMNT via triterpene degradation in Arabidopsis roots. Plant Cell 27:874–890CrossRefGoogle Scholar
  56. Srivastava S, Conlan XA, Adholeya A, Cahill DM (2016) Elite hairy roots of Ocimum basilicum as a new source of rosmarinic acid and antioxidants. Plant Cell Tiss Org Cult 126:19–32CrossRefGoogle Scholar
  57. Tada H, Murakami Y, Omoto T, Shimomura K, Ishimaru K (1996) Rosmarinic acid and related phenolics in hairy root cultures of Ocimum basilicum. Phytochemistry 42:431–434CrossRefGoogle Scholar
  58. Tava A, Scotti C, Avato P (2011) Biosynthesis of saponins in the genus Medicago. Phytochem Rev 10:459–469CrossRefGoogle Scholar
  59. Thimmappa R, Geisler K, Louveau T, O’Maille P, Osbourn A (2014) Triterpene biosynthesis in plants. Annu Rev Plant Biol 65:225–257CrossRefGoogle Scholar
  60. Torre S, Tattini M, Brunetti C, Guidi L, Gori A, Marzano C, Landi M, Sebastiani F (2016) De novo assembly and comparative transcriptome analyses of red and green morphs of sweet basil grown in full sunlight. PLoS ONE 11:e0160370CrossRefGoogle Scholar
  61. Tsubaki S, Sugimura K, Teramoto Y, Yonemori K, Azuma J (2013) Cuticular membrane of Fuyu persimmon fruit is strengthened by triterpenoid nanofillers. PLoS ONE 8:e75275CrossRefGoogle Scholar
  62. Upadhyay AK, Chacko AR, Gandhimathi A, Ghosh P, Harini K, Joseph AP, Joshi AG, Karpe SD, Kaushik S, Kuravadi N, Lingu CS, Mahita J, Malarini R, Malhotra S, Malini M, Mathew OK, Mutt E, Naika M, Nitish S, Pasha SN, Raghavender US, Rajamani A, Shilpa S, Shingate PN, Singh HR, Sukhwal A, Sunitha MS, Sumathi M, Ramaswamy S, Gowda M, Sowdhamini R (2015) Genome sequencing of herb Tulsi (Ocimum tenuiflorum) unravels key genes behind its strong medicinal properties. BMC Plant Biol 15(1)Google Scholar
  63. Wang Q, Reddy VA, Panicker D, Mao HZ, Kumar N, Rajan C, Venkatesh PN, Chua NH, Sarojam R (2016) Metabolic engineering of terpene biosynthesis in plants using a trichome-specific transcription factor MsYABBY5 from spearmint (Mentha spicata). Plant Biotechnol J 14:1619–1632CrossRefGoogle Scholar
  64. Wendt KU, Poralla K, Schulz GE (1997) Structure and function of a squalene cyclase. Science 277:1811–1815CrossRefGoogle Scholar
  65. Xu R, Fazio GC, Matsuda SP (2004) On the origins of triterpenoid skeletal diversity. Phytochem 65(3):261–291CrossRefGoogle Scholar
  66. Xue Z, Xu X, Zhou Y, Wang X, Zhang Y, Liu D, Zhao B, Duan L, Qi X (2018) Deficiency of a triterpene pathway results in humidity-sensitive genic male sterility in rice. Nat Communication 9(1):604CrossRefGoogle Scholar
  67. Zhan X, Yang L, Wang D, Zhu JK, Lang Z (2016) De novo assembly and analysis of the transcriptome of Ocimum americanum var. pilosum under cold stress. BMC Genom 17:209CrossRefGoogle Scholar
  68. Zhang DM, Xu HG, Wang L, Li YJ, Sun PH, Wu XM, Wang GJ, Chen WM, Ye WC (2015) Betulinic acid and its derivatives as potential antitumor agents. Med Res Rev 35:1127–1155fCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Biotechnology DivisionCSIR-Central Institute of Medicinal and Aromatic PlantsLucknowIndia

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