Diterpene synthases of the biosynthetic system of medicinally active diterpenoids in Marrubium vulgare

Plant Journal

Volumn 79, Issue 6, 2014, Pages 914-927

  Zerbe, Philipp ^a   Chiang, Angela ^a   Dullat, Harpreet ^a   O'Neil Johnson, Mark ^b   Starks, Courtney ^b   Hamberger, Björn ^c   Bohlmann, Jörg ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b Sequoia Sciences Inc   (United States)

^c UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

diterpene synthase; diterpenoid biosynthesis; marrubiin; Marrubium vulgare; medicinal plants; natural product biosynthesis; plant specialized metabolism

Indexed keywords

BIOCHEMISTRY; BIOSYNTHESIS; ESCHERICHIA COLI; LIPIDS; METABOLISM; NUCLEAR MAGNETIC RESONANCE; OLEFINS; PHYSIOLOGY; REACTION INTERMEDIATES; SCAFFOLDS;

DITERPENOID; MARRUBIIN; MARRUBIUM VULGARE; MEDICINAL PLANTS; NATURAL PRODUCTS; SYNTHASES;

PLANTS (BOTANY);

COPALYL DIPHOSPHATE; DITERPENE; ENT-KAURENE SYNTHETASE A; ENT-KAURENE SYNTHETASE B; LABDANE; MANOYL OXIDE; MARRUBIIN; MILTIRADIENE; ORGANOPHOSPHATE; TRANSFERASE; VEGETABLE PROTEIN;

AMINO ACID SEQUENCE; CHEMISTRY; ENZYMOLOGY; ESCHERICHIA COLI; GENETICS; MARRUBIUM; MEDICINAL PLANT; METABOLISM; MOLECULAR GENETICS; PHYLOGENY;

ALKYL AND ARYL TRANSFERASES; AMINO ACID SEQUENCE; DITERPENES; ESCHERICHIA COLI; MARRUBIUM; MOLECULAR SEQUENCE DATA; ORGANOPHOSPHATES; PHYLOGENY; PLANT PROTEINS; PLANTS, MEDICINAL;

EID: 84907018134     PISSN: 09607412     EISSN: 1365313X     Source Type: Journal    
DOI: 10.1111/tpj.12589     Document Type: Article

References (62)

1. Ajikumar, P.K., Xiao, W.H., Tyo, K.E., Wang, Y., Simeon, F., Leonard, E., Mucha, O., Phon, T.H., Pfeifer, B., and, Stephanopoulos, G., (2010) Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science, 330, 70-74.
2. Anisimova, M., Gil, M., Dufayard, J.F., Dessimoz, C., and, Gascuel, O., (2011) Survey of branch support methods demonstrates accuracy, power, and robustness of fast likelihood-based approximation schemes. Syst. Biol. 60, 685-699.
3. Belhattab, R., and, Larous, L., (2006) Essential oil composition and glandular trichomes of Marrubium vulgare L. growing in wild Algeria. J. Essent. Oil Res. 18, 369-373.
4. Bohlmann, J., and, Keeling, C.I., (2008) Terpenoid biomaterials. Plant J. 54, 656-669.
5. Boudejal, A., Henchiri, C., Siracusa, L., Sari, M., and, Ruberto, G., (2012) Compositional analysis and in vivo anti-diabetic activity of wild Algerian Marrubium vulgare L. infusion. Filoterapia, 83, 286-292.
6. Brückner, K., and, Tissier, A., (2013) High-level diterpene production by transient expression in Nicotiana benthamiana. Plant Methods, 9, 46.
7. Brückner, K., Božic̈, D., Manzano, D., Papaefthimiou, D., Pateraki, I., Scheler, U., Ferrer, A., de Vos, R.C., Kanellis, A.K., and, Tissier, A., (2014) Characterization of two genes for the biosynthesis of abietane-type diterpenes in rosemary (Rosmarinus officinalis) glandular trichomes. Phytochemistry, 101, 52-64.
8. Caniard, A., Zerbe, P., Legrand, S., Cohade, A., Valot, N., Magnard, J.L., Bohlmann, J., and, Legendre, L., (2012) Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L) and their relevance for perfume manufacture. BMC Plant Biol. 12, 119.
9. Chen, F., Tholl, D., Bohlmann, J., and, Pichersky, E., (2011) The family of terpene synthases in plants, a mid-size family of genes for specialized metabolism that is highly diversified throughout the kingdom. Plant J. 66, 212-229.
10. Dai, Z., Liu, Y., Huang, L., and, Zhang, X., (2012) Production of miltiradiene by metabolically engineered Saccharomyces cerevisiae. Biotechnol. Bioeng. 109, 2845-2853.
11. De Luca, V., Salim, V., Atsumi, S.M., and, Yu, F., (2012) Mining the biodiversity of plants, a revolution in the making. Science, 336, 1658-1661.
12. Demetzos, C., Kolocouris, A., and, Anastasakia, T., (2002) A simple and rapid method for the differentiation of C-13 manoyl oxide epimers in biologically important samples using GC-MS analysis supported with NMR spectroscopy and computational chemistry results. Bioorg. Med. Chem. Lett. 12, 3605-3609.
13. Dendougui, H., Seghir, S., Belloum, Z., Benayache, F., Leon, F., Brouard, I., Bermejo, J., and, Benayache, S., (2011) A new labdane diterpene and other constituents from Marrubium deserti Noe ex coss. Rec. Nat. Prod. 5, 300-304.
14. Deschamp, J., Hermant, T., and, Riant, O., (2012) An easy route toward enantio-enriched polycyclic derivatives via an asymmetric domino conjugate reduction-aldol cyclization catalyzed by a chiral Cu(I) complex. Tetrahedron, 68, 3457-3467.
15. El Bardai, S., Hamaide, M.-C., Lyoussi, B., Quetin-Leclercq, J., Morel, N., and, Wibo, M., (2004) Marrubenol interacts with the phenylalkylamine binding site of the L-type calcium channel. Eur. J. Pharmacol. 492, 269-272.
16. Emanuelsson, O., Nielsen, H., and, von Heijne, G., (1999) ChloroP, a neural network-based method for predicting chloroplast transit peptides and their cleavage sites. Protein Sci. 8, 978-984.
17. Emanuelsson, O., Brunak, S., von Heijne, G., and, Nielsen, H., (2007) Locating proteins in the cell using TargetP, SignalP, and related tools. Nature Protoc. 2, 953-971.
18. Falara, V., Pichersky, E., and, Kanellis, A.K., (2010) A copal-8-ol diphosphate synthase from the angiosperm Cistus creticus subsp. creticus is a putative key enzyme for the formation of pharmacologically active, oxygen-containing labdane-type diterpenes. Plant Physiol. 154, 301-310.
19. Gao, W., Hillwig, M.L., Huang, L., Cui, G., Wang, X., Kong, J., Yang, B., and, Peters, R.J., (2009) A functional genomics approach to tanshinone biosynthesis provides stereochemical insights. Org. Lett. 11, 5170-5173.
20. Gao, Y., Honzatko, R.B., and, Peters, R.J., (2012) Terpenoid synthase structures, a so far incomplete view of complex catalysis. Nat. Prod. Rep. 29, 1153-1175.
21. Guo, J., Zhou, Y.J., Hillwig, M.L., et al. (2013) CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts. Proc. Natl Acad. Sci. USA, 110, 12108-12113.
22. Hall, D.E., Zerbe, P., Jancsik, S., Quesada, A.L., Dullat, H., Madilao, L.L., Yuen, M., and, Bohlmann, J., (2013) Evolution of conifer diterpene synthases, diterpene resin acid biosynthesis in lodgepole pine and jack pine involves monofunctional and bifunctional diterpene synthases. Plant Physiol. 161, 600-616.
23. Harris, L.J., Saparno, A., Johnston, A., Prisic, S., Xu, M., Allard, S., Kathiresan, A., Ouellet, T., and, Peters, R.J., (2005) The maize An2 gene is induced by Fusarium attack and encodes an ent-copalyl diphosphate synthase. Plant Mol. Biol. 59, 881-894.
24. Henderson, M.S., and, McCrindle, R., (1969) Premarrubiin. A diterpenoid from Marrubium vulgare L. J. Chem. Soc. 15, 2014-2015.
25. Hillwig, M.L., Mann, F.M., and, Peters, R.J., (2011a) Diterpenoid biopolymers, new directions for renewable materials engineering. Biopolymers, 95, 71-76.
26. Hillwig, M.L., Xu, M., Toyomasu, T., Tiernan, M.S., Wei, G., Cui, G., Huang, L., and, Peters, R.J., (2011b) Domain loss has independently occurred multiple times in plant terpene synthase evolution. Plant J. 68, 1051-1060.
27. ++ antagonist potential of marrubiin, a labdane type diterpene from Phlomis bracteosa. J. Pharmacy Res. 4, 178-180.
28. Keeling, C.I., Dullat, H.K., Yuen, M., Ralph, S.G., Jancsik, S., and, Bohlmann, J., (2010) Identification and functional characterization of monofunctional ent-copalyl diphosphate and ent-kaurene synthases in white spruce reveal different patterns for diterpene synthase evolution for primary and secondary metabolism in gymnosperms. Plant Physiol. 152, 1197-1208.
29. Keeling, C.I., Weisshaar, S., Ralph, S.G., Jancsik, S., Hamberger, B., Dullat, H.K., and, Bohlmann, J., (2011) Transcriptome mining, functional characterization, and phylogeny of a large terpene synthase gene family in spruce (Picea spp.). BMC Plant Biol. 11, 43.
30. Knöss, W., and, Zapp, J., (1997) Accumulation of furanic diterpenes in Marrubium vulgare and Leonurus cardiaca. Planta Med. 64, 357-361.
31. Köksal, M., Potter, K., Peters, R.J., and, Christianson, D.W., (2014) 1.55Å-resolution structure of ent-copalyl diphosphate synthase and exploration of general acid function by site-directed mutagenesis. Biochim. Biophys. Acta, 1840, 184-190.
32. Kolosova, N., Miller, B., Ralph, S., Ellis, B.E., Douglas, C., Ritland, K., and, Bohlmann, J., (2004) Isolation of high-quality RNA from gymnosperm and angiosperm trees. Biotechniques, 36, 821-824.
33. Mafu, S., Hillwig, M.L., and, Peters, R.J., (2011) A novel labda-7,13E-dien-15-ol-producing bifunctional diterpene synthase from Selaginella moellendorffii. Chembiochem, 12, 1984-1987.
34. Mangoni, L., Adinolfi, M., Laonigro, G., and, Caputo, R., (1972) Synthesis of marrubiin. Tetrahedron, 28, 611-621.
35. Martin, D.M., Fäldt, J., and, Bohlmann, J., (2004) Functional characterization of nine Norway Spruce TPS genes and evolution of gymnosperm terpene synthases of the TPS-d subfamily. Plant Physiol. 135, 1908-1927.
36. Meyre-Silva, C., and, Cechinel-Filho, V., (2010) A review of the chemical and pharmacological aspects of the genus Marrubium. Curr. Pharm. Des. 16, 3503-3518.
37. Meyre-Silva, C., Yunes, R.A., Schlemper, V., Campos-Buzzi, F., and, Cechinel-Filho, V., (2005) Analgesic potential of marrubiin derivatives, a bioactive diterpene present in Marrubium vulgare (Lamiaceae). Il Farmaco, 60, 321-326.
38. Mnonopi, N., Levendal, R.A., Davies-Coleman, M.T., and, Frost, C.L., (2011) The cardioprotective effects of marrubiin, a diterpenoid found in Leonotis leonurus extracts. J. Ethnopharmacol. 138, 67-75.
39. Mnonopi, N., Levendal, R.A., Mzilikazi, N., and, Frost, C.L., (2012) Marrubiin, a constituent of Leonotis leonurus, alleviates diabetic symptoms. Phytomedicine, 19, 488-493.
40. Morgenstern, B., (2004) DIALIGN, multiple DNA and protein sequence alignment at BiBiServ. Nucl. Acids Res. 32, W33-W36.
41. Morrone, D., Lowry, L., Determan, M.K., Hershey, D.M., Xu, M., and, Peters, R.J., (2010) Increasing diterpene yield with a modular metabolic engineering system in E. coli, comparison of MEV and MEP isoprenoid precursor pathway engineering. Appl. Microbiol. Biotechnol. 85, 1893-1906.
42. Morrone, D., Hillwig, M.L., Mead, M.E., Lowry, L., Fulton, D.B., and, Peters, R.J., (2011) Evident and latent plasticity across the rice diterpene synthase family with potential implications for the evolution of diterpenoid metabolism in the cereals. Biochem. J. 435, 589-595.
43. Pateraki, I., Andersen-Ranberg, J., Hamberger, B., Heskes, A.M., Martens, H.J., Zerbe, P., Bach, S.S., Møller, B.L., Bohlmann, J., and, Hamberger, B., (2014) Manoyl oxide (13R), the biosynthetic precursor of forskolin, is synthesized in specialized root cork cells in Coleus forskohlii. Plant Physiol. 164, 1222-1236.
44. Peters, R.J., (2010) Two rings in them all, The labdane-related diterpenoids. Nat. Prod. Rep. 27, 1521.
45. Peters, R.J., Flory, J.E., Jetter, R., Ravn, M.M., Lee, H.J., Coates, R.M., and, Croteau, R.B., (2000) Abietadiene synthase from grand fir (Abies grandis), characterization and mechanism of action of the " pseudomature" recombinant enzyme. Biochemistry, 39, 15592-15602.
46. Popoola, O.K., Elbagory, A.M., Ameer, F., and, Hussein, A.A., (2013) Marrubiin. Molecules, 18, 9049-9060.
47. Salei, L.A., Popa, D.P., Doleish, L., and, Lazur'evskii, G.W., (1967) The structure of peregrinol, a diterpenoid from Marrubium peregrinum. Khim. Prir. Soedin. 8, 90-95.
48. Sallaud, C., Giacalone, C., Töpfer, R., Goepfert, S., Bakaher, N., Rösti, S., and, Tissier, A., (2012) Characterization of two genes for the biosynthesis of the labdane diterpene Z-abienol in tobacco (Nicotiana tabacum) glandular trichomes. Plant J. 72, 1-17.
49. Schalk, M., Pastore, L., Mirata, M.A., Khim, S., Schouwey, M., Deguerry, F., Pineda, V., Rocci, L., and, Daviet, L., (2012) Toward a biosynthetic route to sclareol and amber odorants. J. Am. Chem. Soc. 134, 18900-18903.
50. Sugai, Y., Ueno, Y., Hayashi, K., Oogami, S., Toyomasu, T., Matsumoto, S., Natsume, M., Nozaki, H., and, Kawaide, H., (2011) Enzymatic (13)C labeling and multidimensional NMR analysis of miltiradiene synthesized by bifunctional diterpene cyclase in Selaginella moellendorffii. J. Biol. Chem. 286, 42840-42847.
51. Sun, T.P., and, Kamiya, Y., (1994) The Arabidopsis GA1 locus encodes the cyclase ent-kaurene synthetase A of gibberellin biosynthesis. Plant Cell, 6, 1509-1518.
52. Voinnet, O., Rivas, S., Mestre, P., and, Baulcombe, D., (2003) An enhanced transient expression system in plants based on suppression of gene silencing by the p19 protein of tomato bushy stunt virus. Plant J. 33, 949-956.
53. Wu, Y., Zhou, K., Toyomasu, T., et al. (2012) Functional characterization of wheat copalyl diphosphate synthases sheds light on the early evolution of labdane-related diterpenoid metabolism in the cereals. Phytochemistry, 84, 40-46.
54. Wurch, T., Lestienne, F., and, Pauwels, P.J., (1998) A modified overlap extension PCR method to create chimeric genes in the absence of restriction enzymes. Biotechnol. Tech. 12, 653-657.
55. Xu, M., Wilderman, P.R., Morrone, D., Xu, J., Roy, A., Margis-Pinheiro, M., Upadhyaya, N.M., Coates, R.M., and, Peters, R.J., (2007) Functional characterization of the rice kaurene synthase-like gene family. Phytochemistry, 68, 312-326.
56. Yamaguchi, S., Sun, T.P., Kawaide, H., and, Kamiya, Y., (1998) The GA2 locus of Arabidopsis thaliana encodes ent-kaurene synthase of gibberellin biosynthesis. Plant Physiol. 116, 1271-1278.
57. Zerbe, P., and, Bohlmann, J., (2014) Metabolic engineering of terpene synthases of conifer defense, bioproducts, biofuels and perfumes. Recent Adv. Phytochem. 44, 85-107.
58. Zerbe, P., Chiang, A., Yuen, M., Hamberger, B., Hamberger, B., Draper, J.A., Britton, R., and, Bohlmann, J., (2012a) Bifunctional cis-abienol synthase from Abies balsamea discovered by transcriptome sequencing and its implications for diterpenoid fragrance production. J. Biol. Chem. 287, 12121-12131.
59. Zerbe, P., Chiang, A., and, Bohlmann, J., (2012b) Mutational analysis of white spruce (Picea glauca) ent-kaurene synthase (PgKS) reveals common and distinct mechanisms of conifer diterpene synthases of general and specialized metabolism. Phytochemistry, 74, 30-39.
60. Zerbe, P., Hamberger, B., Yuen, M.M., Chiang, A., Sandhu, H.K., Madilao, L.L., Nguyen, A., Hamberger, B., Bach, S.S., and, Bohlmann, J., (2013) Gene discovery of modular diterpene metabolism in nonmodel systems. Plant Physiol. 162, 1073-1091.
61. Zhou, Y.J., Gao, W., Rong, Q., et al. (2012a) Modular pathway engineering of diterpenoid synthases and the mevalonic acid pathway for miltiradiene production. J. Am. Chem. Soc. 134, 3234-3241.
62. Zhou, K., Xu, M., Tiernan, M., et al. (2012b) Functional characterization of wheat ent-kaurene(-like) synthases indicates continuing evolution of labdane-related diterpenoid metabolism in the cereals. Phytochemistry, 84, 47-55.