Tropine Forming Tropinone Reductase Gene from Withania somnifera (Ashwagandha): Biochemical Characteristics of the Recombinant Enzyme and Novel Physiological Overtones of Tissue-Wide Gene Expression Patterns

PLoS ONE

Volumn 8, Issue 9, 2013, Pages

  Kushwaha, Amit Kumar ^a   Sangwan, Neelam Singh ^a   Trivedi, Prabodh Kumar ^b   Negi, Arvind Singh ^a   Misra, Laxminarain ^a   Sangwan, Rajender Singh ^a,c  

^a CSIR CENTRAL INSTITUTE OF MEDICINAL AND AROMATIC PLANTS   (India)

^b CSIR NATIONAL BOTANICAL RESEARCH INSTITUTE   (India)

^c INSTITUTE OF NANO SCIENCE AND TECHNOLOGY   (India)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID; CARBON 14; JASMONIC ACID METHYL ESTER; RECOMBINANT ENZYME; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; SALICYLIC ACID; SUCROSE; TROPANE; TROPANONE; TROPINE; TROPINONE REDUCTASE; UNCLASSIFIED DRUG; VEGETABLE PROTEIN;

ARTICLE; BERRY; BINDING SITE; BIOCHEMISTRY; BIOSYNTHESIS; CATALYSIS; CONTROLLED STUDY; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME KINETICS; ENZYME MECHANISM; ENZYME STRUCTURE; ESCHERICHIA COLI; FEEDING; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; IN VIVO STUDY; METABOLISM; MOLECULAR CLONING; NONHUMAN; NUCLEOTIDE SEQUENCE; PH; PHYTOCHEMISTRY; PLANT DAMAGE; PLANT GENE; PLANT LEAF; PLANT PHYSIOLOGY; PLANT ROOT; PLANT TISSUE; POPULATION ABUNDANCE; SHOOT; TROPINONE REDUCTASE GENE; UPREGULATION; WITHANIA SOMNIFERA;

ALCOHOL OXIDOREDUCTASES; AMINO ACID SEQUENCE; BIOCATALYSIS; BIOSYNTHETIC PATHWAYS; CLONING, MOLECULAR; ELECTROPHORESIS, POLYACRYLAMIDE GEL; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENES, PLANT; HYDROGEN-ION CONCENTRATION; KINETICS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; ORGAN SPECIFICITY; PHYLOGENY; RECOMBINANT PROTEINS; SEQUENCE ANALYSIS, PROTEIN; STRUCTURAL HOMOLOGY, PROTEIN; SUBSTRATE SPECIFICITY; TROPANES; WITHANIA;

EID: 84884569638     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0074777     Document Type: Article

References (58)

1. Sangwan RS, Chaurasiya ND, Misra LN, Lal P, Uniyal GC, et al. (2004) Phytochemical variability in commercial herbal products and preparations of Ashwagandha (Withania somnifera). Curr Sci 86: 461-465.
2. Tuli R, Sangwan RS (2010) Ashwagandha (Withania somnifera) - a model Indian medicinal plant. Council of Scientific and Industrial Research (CSIR), New Delhi, ISBN 978-93-80235-29-5.
3. Mirjalili MH, Moyano E, Bonfill M, Cusido RM, Palazón J, (2010) Steroidal lactones from Withania somnifera, An ancient plant for novel medicine. Molecules 14: 2373-2393.
4. Chatterjee S, Srivastava S, Khalid A, Singh N, Sangwan RS, et al. (2010) Comprehensive metabolic fingerprinting of Withania somnifera leaf and root extracts. Phytochemistry 71: 1085-1094.
5. Jayaprakasam B, Strasburg GA, Nair MG, (2004) Potent lipid peroxidation inhibitors from Withania somnifera fruits. Tetrahedron 60: 3109-3121.
6. Misra LN, Misra P, Pandey A, Sangwan RS, Sangwan NS, (2012) 1,4 dioxane and ergosterol derivatives from Withania somnifera roots. J Asian Nat Prod Res 14: 39-45.
7. Gupta P, Goel R, Pathak S, Srivastava A, Singh SP, et al. (2013) De novo assembly, functional annotation and comparative analysis of Withania somnifera leaf and root transcriptomes to identify putative genes involved in the withanolides biosynthesis. PLoS ONE 8(5): e62714.
8. Chen LX, He H, Qui F, (2011) Natural withanolides: an overview. Nat Prod Rep 28: 705-740.
9. Misra L, Lal P, Sangwan RS, Sangwan NS, Uniyal GC, et al. (2005) Unusually sulfated and oxygenated steroids from Withania somnifera. Phytochemistry 66: 2702-2707.
10. Lal P, Misra L, Sangwan RS, Tuli R, (2006) New withanolides from fresh berries of Withania somnifera. Z Naturforsch B 61: 1143-1147.
11. Cordell GA, Quinn-Beattie ML, Farnsworth NR, (2001) The potential of alkaloids in drug discovery. Phytother. Res. 15: 183-205.
12. Newman DJ, Cragg GM, Snader KM, (2003) Natural products as sources of new drugs over the period 1981-2002. J Nat Prod 66: 1022-1037.
13. Ortholand JY, Ganesan A, (2004) Natural products and combinatorial chemistry: back to the future. Curr Opin Chem Biol 8: 271-280.
14. Cordell GA, Colvard MD, (2012) Natural products and traditional medicine: turning on a paradigm. J Nat Prod 75: 514-525.
15. Grynkiewicz G, Gadzikowska M, (2008) Tropane alkaloids as medicinally useful natural products and their synthetic derivatives as new drugs. Pharma Rep 60: 439-463.
16. Bekkouche K, Daali Y, Cherkaoui S, Veuthey J, Christen P, (2001) Calystegine distribution in some solanaceous species. Phytochemistry 58: 455-462.
17. Majumdar DN, (1955) Indian medicinal plants. Part II. Withania somnifera. J Ind Inst Sci 16A: 29-33.
18. Mandal C, Dutta A, Mallick A, Chandra S, Misra L, et al. (2008) Withaferin A induces apoptosis by activating p38 mitogen-activated protein kinase signaling cascade in leukemic cells of lymphoid and myeloid origin in a transcription-dependent manner through mitochondrial death cascade. Apoptosis 13: 1450-1464.
19. Mondal S, Mandal C, Sangwan RS, Chandra S, Mandal C, (2010) Withanolide D induces apoptosis in leukemia by targeting the activation of neutral sphingomyelinase-ceramide cascade mediated by synergistic activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. Mol Cancer 9: 239.
20. Kushwaha S, Soni VK, Singh PK, Bano N, Kumar A, et al. (2012) Withania somnifera chemotypes NMITLI 101R, NMITLI 118R, NMITLI 128R and withaferin A protect Mastomys coucha rom Brugia malayi infection. Parasite Immunol 34: 199-209.
21. Kushwaha S, Roy S, Maity R, Mallick A, Soni VK, et al. (2012) Chemotypical variations in Withania somnifera lead to differentially modulated immune response in BALB/c mice. Vaccine 30: 1083-1093.
22. Mandal S, Bhattacharya K, Mallick A, Sangwan RS, Mandal C, (2012) Bak compensated for Bax in p53-null cells to release cytochrome c for the initiation of mitochondrial signaling during withanolide D-induced apoptosis. PLoS ONE 7(3): e34277.
23. Mandal S, Roy S, Maity R, Mallick A, Sangwan RS, et al. (2012) Withanolide D, carrying the baton of Indian Rasayana herb as a lead candidate of antileukemic agent in modern medicine. Adv Exp Med Biol 749: 295-312.
24. Sangwan RS, Chaurasiya ND, Lal P, Misra L, Tuli R, et al. (2008) Root-contained withanolide A is inherently de novo synthesized within roots in Ashwagandha (Withania somnifera). Physiol Plant 133: 278-287.
25. Chaurasiya ND, Sangwan NS, Sabir F, Misra LN, Sangwan RS, (2012) Withanolide biosynthesis recruits both mevalonate and DOXP pathways of isoprenogenesis in Ashwagandha Withania somnifera L. (Dunal). Plant Cell Rep 31: 1889-1897.
26. Sharma LK, Madina BR, Chaturvedi P, Sangwan RS, Tuli R, (2007) Molecular cloning and characterization of one member of 3beta-hydroxy sterol glucosyltransferase gene family in Withania somnifera. Arch Biochem Biophys 460: 48-55.
27. Madina BR, Sharma LK, Chaturvedi P, Sangwan RS, Tuli R, (2007) Purification and characterization of a novel glucosyltransferase specific to 27ß-hydroxy steroidal lactones from Withania somnifera and its role in stress responses. Biochim Biophys Act 1774: 1199-1207.
28. Gupta P, Agarwal AV, Akhtar N, Sangwan RS, Singh SP, et al. (2013) Cloning and characterization of 2-C-methyl-D-erythritol-4-phosphate pathway genes for isoprenoid biosynthesis from Indian ginseng, Withania somnifera. Protoplasma 250: 285-295.
29. Gupta P, Akhtar N, Tewari SK, Sangwan RS, Trivedi PK, (2011) Differential expression of farnesyl diphosphate synthase gene from Withania somnifera in different chemotypes and in response to elicitors. Plant Growth Regul 65: 93-100.
30. Bekkouche KY, Cherkaoui S, Veuthey J, Christen P, (2001) Calystegine distribution in some Solanaceae species. Phytochemistry 58: 455-462.
31. Keiner R, Drager B, (2000) Calystegine distribution in potato (Solanum tuberosum) tubers and plants. Plant Sci 150: 171-179.
32. Griffin WJ, Lin GD, (2000) Chemotaxonomy and geographical distribution of tropane alkaloids. Phytochemistry 53: 627-637.
33. Oppermann U, Filling C, Hult M, Shafqat N, Wua X, et al. (2003) Short-chain dehydrogenases/reductases (SDR): the 2002 update. Chem Biol Interact 143-144: 247-253.
34. Nakajima K, Yamashita A, Akama H, Nakatsu T, Kato H, et al. (1998) Crystal structures of two tropinone reductases: different reaction stereospecificities in the same protein fold. Proc Nat Acad Sci 95: 4876-81.
35. Hashimoto T, Nakajima K, Ongena G, Yamada Y, (1992) Two tropinone reductases with distinct stereospecificities from cultured roots of Hyoscyamus niger. Plant Physiol 100: 836-845.
36. Yamada Y, Hashimoto T, (1990) Possibilities for improving yields of secondary metabolites in plant cell cultures. Curr Plant Sci Biotech Agric 9: 547-556.
37. Kutchan M, Frick S, Weid M, (2008) Engineering plant alkaloid biosynthetic pathways: progress and prospects. Adv Plant Biochem Mol Biol 1: 293-310.
38. Nakajima K, Hashimoto T, Yamada Y (1993a) Two tropinone reductases with different stereospecificities are short-chain dehydrogenases evolved from a common ancestor. Proc Natl Acad Sci USA 90; 9591-9595.
39. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ, (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265-275.
40. Nakajima K, Hashimoto T, Yamada Y, (1994) Opposite stereospecificity of two tropinone reductases is conferred by the substrate-binding sites. J Biol Chem 269: 11695-11698.
41. Nakajima K, Kato H, Oda J, Yamada Y, Hashimoto T, (1999) Site-directed mutagenesis of putative substrate-binding residues reveals a mechanism controlling the different stereospecificities of two tropinone reductases. J Biol Chem 274: 16563-16568.
42. Kai G, Li L, Jiang Y, Yan X, Zhang Y, et al. (2009) Molecular cloning and characterization of two tropinone reductases in Anisodus acutangulus and enhancement of tropane alkaloid production in AaTRI-transformed hairy roots. Biotech Appl Biochem 54; 177-186.
43. Nakajima K, Hashimoto T, Yamada Y, (1993b) cDNA encoding Tropinone reductase-II from Hyoscyamus niger. Plant Physiol 103: 1465-1466.
44. Nakajima K, Hashimoto T, Yamada Y, (1994) Opposite stereospecificity of two tropinone reductases is conferred by the substrate-binding sites. J Biol Chem 269: 11695-11698.
45. Kaiser H, Richter U, Keiner R, Brabant A, Hause B, et al. (2006) Immunolocalisation of two tropinone reductases in potato (Solanum tuberosum L.) root, stolon, and tuber sprouts. Planta 225: 127-137.
46. Drager B, Hashimoto T, Yamada Y, (1988) Purification and characterization of pseudotropine forming tropinone reductase from Hyoscyamus niger root cultures. Agric Biol Chem 52: 2663-2667.
47. Sangwan RS, Sangwan NS, Luthra R, (1993) Metabolism of acyclic monoterpenes: partial purification and properties of geraniol dehydrogenase from Lemongrass (Cymbopogon flexuosus Stapf.) leaves. J Plant Physiol 142: 129-134.
48. Brock A, Brandt W, Drager B, (2008) The functional divergence of short-chain dehydrogenases involved in tropinone reduction. Plant J 54: 388-401.
49. Chen W, Cheng X, Zhou Z, Liu J, Wang H, (2013) Molecular cloning and characterization of a tropinone reductase from Dendrobium nobile Lindl. Mol Biol Rep. 40: 1145-1154.
50. Cheng X, Chen W, Zhou Z, Liu J, Wang H (2013) Functional characterization of a novel tropinone reductase-like gene in Dendrobium nobile Lindl. J Plant Physiol dx.doi.org/10.1016/j.jplph.2013.02.007.
51. Wink M, (2003) Evolution of secondary metabolites from an ecological and molecular phylogenetic perspective. Phytochemistry 64: 3-19.
52. Geissler R, Brandt W, Ziegler J, (2007) Molecular modeling and site-directed mutagenesis reveal the benzylisoquinoline binding site of the short-chain dehydrogenase/reductase salutaridine reductase. Plant Physiol 143: 1493-1503.
53. Dehghan E, Ahmadi FS, Ravandi EG, Reed DW, Covello PS, et al. (2013). A typical pattern of accumulation of scopolamine and other tropane alkaloids and expression of alkaloid pathway genes in Hyoscyamus senecionis. Plant Physiol Biochem. dx.doi.org/10.1016/j.plaphy.2013.05.007.
54. Peacock SM, Leyerle DB, Dawson RF, (1944) Alkaloid Accumulation in Reciprocal Grafts of Datura Stramonium with tobacco and tomato. Am J Bot 31: 463-466.
55. Nakajima K, Hashimoto T, (1999) Two tropinone reductases, that catalyze opposite stereospecific reductions in tropane alkaloid biosynthesis, are localized in plant root with different cell-specific patterns. Plant Cell Physiol 40: 1099-1107.
56. Kushwaha AK, Sangwan NS, Tripathi S, Sangwan RS, (2013) Molecular cloning and catalytic characterization of a recombinant tropine biosynthetic tropinone reductase from Withania coagulans leaf. Gene 516: 238-247.
57. Keiner R, Kaiser H, Nakajima K, Hashimoto T, Dräger B, (2002) Molecular cloning, expression and characterization of Tropinone reductase II, an enzyme of the SDR family in Solanum tuberosum (L.). Plant Mol Biol 48: 299-308.
58. Portsteffen A, Drager B, Nahrstedt A, (1994) The reduction of tropinone in Datura stramonium root cultures by two specific reductases. Phytochemistry 37: 391-400.