Arora R. (ed.) Medicinal Plant Biotechnology
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354 Camptothecins: SAR, QSAR and Biotechnology
It is interesting to note that the isolation of CPT-producing organisms in the future, may
provide an easily accessible source for the production of CPT. In a recent study, an
endophytic fungal producing CPT has been isolated from the inner bark of the plant
Nothapodytes foetida from the western coast of India (Puri et al., 2005) and its
immunomodulatory, antioxidant activity (Amna et al., 2007; Arora et al., 2010) and
radioprotective efficacy were established (Arora et al., unpublished work).
The expression of biosynthetic pathways
The genes of some key enzymes such as strictosidine synthase, tryptophan decarboxylase,
and NADPH: cytochrome P450 reductase are responsible for the biosynthesis of CPT that
have been cloned from hairy roots of Ophiorrhiza pumila. Heterologous expression of the
cDNAs coding for these enzymes expressed in Escherichia coli cells yielded functional
recombinant proteins. This may prove to be an important step towards the genetic
engineering for recombinant CPT biosynthesis in large-scale production (Yamazaki et al.,
2003).
Conclusion
Isolation and structural elucidation of camptothecin (CPT; a natural product) enabled
pharmacological and molecular biological investigations to establish CPT as one of the
lead compounds for bioactivity-based generation of semi-synthetic derivatives e.g.
topotecan and irinotecan, the FDA approved anticancer drugs. SAR and QSAR studies on
CPT analogues may provide key information in further design and development of new
CPT derivatives in order to improve pharmacokinetics, drug resistance and toxicity
profiles. At present, over a dozen new CPT derivatives are in various stages of clinical
trials. The recent advancement in biotechnology has provided a great hope for the
alternative route of CPT production to field cultivation. We hope the biotechnology may
fulfil the demand gap of CPT in the pharmaceutical market in the future.
References
Amna, T., Puri, S.C., Gupta, A., Khajuria, A., Arora, R., Spiteller, M. and Qazi, G.N. (2007)
Immunomodulatory activity of an extract of the novel endophyte Entrophosphora infrequens
isolated from Nothapodytes foetida (Wight) Sleumer. Acta Microbiologica et Immunologica
Hungarica 54(3), 237–260.
Arora, R., Chawla, R., Dhaker, A.S., Adhikari, M., Sharma, J., Jaiswal, S., Gupta, D., Amna, T., Puri,
S.C., Kumar, R., Sharma, A., Sharma, R.K. and Tripathi, R.P. (2010) Pro-antioxidant activities
of fractions of a novel camptothecin-producing endophyte (Entrophosphora infrequens). Trakia
Journal of Sciences 8(2), 1–15.
Bailly, C. (2003) Homocamptothecins: potent topoisomerase I inhibitors and promising anticancer
drugs. Critical Reviews in Oncology/Hematology 45, 91–108.
Burke, T.G. and Mi, Z. (1993) Ethyl substitution at the 7 position extends the half-life of 10-
hydroxycamptothecin in the presence of human serum albumin. Journal of Medicinal Chemistry
36, 2580–2582.
Camptothecins: SAR, QSAR and Biotechnology 355
Cao, Z., Pantazis, P., Mendoza, J., Early, J., Kozielski, A., Harris, N., Vardeman, D., Liehr, J.,
Stehlin, J.S. and Giovanella, B. (2000) Structure-activity relationship of alkyl camptothecin
esters. Annals of the New York Academy of Sciences 922, 122–135.
Carrigan, S.W., Fox, P.C., Wall, M.E., Wani, M. and Bowen, J. (1997) Comparative molecular field
analysis and molecular modeling studies of 20-(S)-camptothecin analogs as inhibitors of DNA
topoisomerase I and anticancer/antitumour agents. Journal of Computer-Aided Molecular
Design 11, 71–78.
Chrencik, J.E., Staker, B.L., Burgin, A.B., Pourquier, P., Pommier, Y., Stewart, L. and Redinbo,
M.R. (2004) Mechanisms of camptothecin resistance by human topoisomerase I mutations.
Journal of Molecular Biology 339, 773–784.
Crow, R.T. and Crothers, D.M. (1992) Structural modifications of camptothecin and effects on
topoisomerase I inhibition. Journal of Medicinal Chemistry 35, 4160–4164.
Dallavalle, S., Delsoldato, T., Ferrari, A., Merlini, L., Penco, S., Carenini, N., Perego, P., De Cesare,
M., Pratesi, G. and Zunino, F. (2000) Novel 7-substituted camptothecins with potent antitumour
activity. Journal of Medicinal Chemistry 43, 3963–3969.
Dallavalle, S., Ferrari, A., Merlini, L., Penco, S., Carenini, N., De Cesare, M., Perego, P., Pratesi, G.
and Zunino, F. (2001) Novel cytotoxic 7-iminomethyl and 7-aminomethyl derivatives of
camptothecin. Bioorganic & Medicinal Chemistry Letters 11, 291–294.
Efferth, T., Fu, Y.-J., Zu, Y.-G., Schwarz, G., Konkimalla, V.S.B. and Wink, M. (2007) Molecular
target-guided tumor therapy with natural products derived from traditional Chinese medicine.
Current Medicinal Chemistry 14, 2024–2032.
Eriksson, L., Jaworska, J., Worth, A.P., Cronin, M.T.D., McDowell, R.M. and Gramatica, P. (2003)
Methods for reliability and uncertainty assessment and for applicability evaluations of
classification- and regression-based QSARs. Environmental Health Perspectives 111, 1361–
1375.
Fuchs, C., Mitchell, E.P. and Hoff, P.M. (2006) Irinotecan in the treatment of colorectal cancer.
Cancer Treatment Reviews 32, 491–503.
Hansch, C. and Verma, R.P. (2007) 20-(S)-camptothecin analogs as DNA topoisomerase I inhibitors:
a QSAR study. ChemMedChem 2, 1807–1813.
Hansch, C., Maloney, P.P., Fujita, T. and Muir, R.M. (1962) Correlation of biological activity of
phenoxyacetic acids with Hammett substituent constants and partition coefficients. Nature 194,
178–180.
Hatefi, A. and Amsden, B. (2002) Camptothecin delivery methods. Pharmaceutical Research 19,
1389–1399.
Hecht, S.M. (2005) Camptothecin: Role of the D and E rings in binding to the topoisomerase I-DNA
covalent binary complex. Current Medicinal Chemistry – Anti-Cancer Agents 5, 353–362.
Hertzberg, R.P., Caranfa, M.J., Holden, K.G., Jakas, D.R., Gallagher, G., Mattern, M.R., Mong,
S.M., Bartus, J.O., Johnson, R.K. and Kingsbury, W.D. (1989) Modification of the
hydroxylactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological
activity. Journal of Medicinal Chemistry 32, 715–720.
Hsiang, Y.H., Lihou, M.G. and Liu, L.F. (1989) Arrest of replication forks by drug-stabilized
topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin.
Cancer Research 49, 5077–5082.
Jew, S.S., Kim, H.J., Kim, M.G., Roh, E.Y., Hong, C.I., Kim, J.K., Lee, J.H., Lee, H. and Park, H.G.
(1999) Synthesis and in vitro cytotoxicity of hexacyclic camptothecin analogs. Bioorganic &
Medicinal Chemistry Letters 9, 3203–3206.
Kim, D.K. and Lee, N. (2002) Recent advances in topoisomerase I-targeting agents, camptothecin
analogues. Mini-Reviews in Medicinal Chemistry 2, 611–619.
Kingsbury, W.D., Boehm, J.C., Jakas, D.R., Holden, K.G., Hecht, S.M., Gallagher, G., Caranfa, M.J.,
McCabe, F.L., Faucette, L.F., Johnson, R.K. and Hertzberg, R.P. (1991) Synthesis of water-
soluble (aminoalkyl)camptothecin analogs: inhibition of topoisomerase I and antitumour
activity. Journal of Medicinal Chemistry 34, 98–107.
356 Camptothecins: SAR, QSAR and Biotechnology
Lavergne, O., Lesueur-Ginot, L., Rodas, F.P. and Bigg, D.C.H. (1997) BN 80245: an E-ring modified
camptothecin with potent antiproliferative and topoisomerase I inhibitory activities. Bioorganic
& Medicinal Chemistry Letters 7, 2235–2238.
Lavergne, O., Lesueur-Ginot, L., Rodas, F.P., Kasprzyk, P.G., Pommier, J., Demarquay, D., Prevost,
G., Ulibarri, G., Rolland, A., Schiano-Liberatore, A.M., Harnett, J., Pons, D., Camara, J. and
Bigg, D.C.H. (1998) Homocamptothecins: Synthesis and antitumour activity of novel E-ring-
modified camptothecin analogs. Journal of Medicinal Chemistry 41, 5410–5419.
Legarza, K. and Yang, L.X. (2005) Novel camptothecin derivatives. In Vivo 19, 283–292.
Legarza, K. and Yang, L.X. (2006) New molecular mechanisms of action of camptothecin-type
drugs. Anticancer Research 26, 3301–3305.
Li, Q.Y., Zu, Y.G., Shi, R.Z. and Yao, L.P. (2006) Review camptothecin: Current perspectives.
Current Medicinal Chemistry 13, 2021–2039.
Liu, L.F., Desai, S.D., Li, T.K., Mao, Y., Sun, M. and Sim, S.P. (2000) Mechanism of action of
camptothecin. Annals of the New York Academy of Sciences 922, 1–10.
Markman, M. (2005) Topotecan as second-line therapy for ovarian cancer: Dosage versus toxicity.
Oncologist 10, 695–697.
Oberlies, N.H. and Kroll, D.J. (2004) Camptothecin and taxol: Historic achievements in natural
products research. Journal of Natural Products 67, 129–135.
Ormrod, D. and Spencer, C.M. (1999) Topotecan: a review of its efficacy in small-cell lung cancer.
Drugs 58, 533–551.
Pan, X.-W., Xu, H.-H., Xin, L., Gao, X. and Lu, Y.-T. (2004) Improvement of growth and
camptothecin yield by altering nitrogen source supply in cell suspension cultures of
Camptotheca acuminata. Biotechnology Letters 26, 1745–1748.
Pavillard, V., Charasson, V., Laroche-Clary, A., Soubeyran, I. and Robert, J. (2004) Cellular
parameters predictive of the clinical response of colorectal cancers to irinotecan. A preliminary
study. Anticancer Research 24, 579–585.
Puri, S.C., Verma, V., Amna, T., Qazi, G.N. and Spiteller, M. (2005) An endophytic fungus from
Nothapodytes foetida that produces camptothecin. Journal of Natural Products 68, 1717–1719.
Soepenberg, O., Sparreboom, A. and Verweij, J. (2003) Clinical studies of camptothecin and
derivatives. The Alkaloids: Chemistry and Biology 60, 1–50.
Srikantaramas, S., Asano, T., Sudo, H., Yamazaki, M., Saito, K. (2007) Camptothecin: Therapeutic
potential and biotechnology. Current Pharmaceutical Biotechnology 8, 196–202.
Sriram, D., Yogeeswari, P., Thirumurugan, R. and Bal, T.R. (2005) Camptothecin and its analogues:
a review on their chemotherapeutic potential. Natural Product Research 19, 393–341.
Subrahmanyam, D., Sarma, V.M., Venkateswarlu, A., Sastry, T.V.R.S., Kulakarni, A.P., Srinivasa,
R.D. and Krishna Reddy, K.V.S.R. (1999a) In vitro cytotoxicity of 5-aminosubstituted 20(S)-
camptothecins. Part 1. Bioorganic & Medicinal Chemistry 7, 2013–2020.
Subrahmanyam, D., Venkateswarlu, A., Rao, K.V., Sastry, T.V.R.S., Vandana, G. and Kumar, S.A.
(1999b) Novel C-ring analogues of 20(S)-camptothecin. Part-2: synthesis and in vitro
cytotoxicity of 5-C-substituted 20(S)-camptothecin analogues. Bioorganic & Medicinal
Chemistry Letters 9, 1633–1638.
Subrahmanyam, D., Sarma, V.M., Venkateswarlu, A., Sastry, T.V., Srinivas, A.S., Krishna, C.V.,
Deevi, D.S., Kumar, S.A., Babu, M.J. and Damodaran, N.K. (2000) Novel C-ring analogues of
20(S)- camptothecin. Part 3: synthesis and their in vitro cytotoxicity of A-, B- and C-ring
analogues. Bioorganic & Medicinal Chemistry Letters 10, 369–371.
Sudo, H., Yamakawa, T., Yamazaki, M., Aimi, N., Saito, K. (2002) Bioreactor production of
camptothecin by hairy root cultures of Ophiorrhiza pumila. Biotechnology Letters 24, 359–363.
Sugimori, M., Ejima, A., Ohsuki, S., Matsumoto, K., Kawato, Y., Yasuoka, M., Tagawa, H. and
Terasawa, H. (1994) Antitumour agents. VI. Synthesis and antitumour activity of ring A-, ring
B-, and ring C-modified derivatives of camptothecin. Heterocycles 38, 81–94.
Tanizawa, A., Kohn, K.W., Kohlhagen, G., Leteurtre, F. and Pommier, Y. (1995) Differential
stabilization of eukaryotic DNA topoisomerase I cleavable complexes by camptothecin
derivatives. Biochemistry 34, 7200–7206.
Camptothecins: SAR, QSAR and Biotechnology 357
Thomas, C.J., Rahier, N.J. and Hecht, S.M. (2004) Camptothecin: current perspectives. Bioorganic &
Medicinal Chemistry 12, 1585–1604.
Uehling, D.E., Nanthakumar, S.S., Croom, D., Emerson, D.L., Leitner, P.P., Luzzio, M.J., McIntyre,
G., Morton, B., Profeta, S., Sisco, J., Sternbach, D.D., Tong, W.Q., Vuong, A. and Besterman,
J.M. (1995) Synthesis, topoisomerase I inhibitory activity, and in vivo evaluation of 11-
azacamptothecin analogs. Journal of Medicinal Chemistry 38, 1106–1118.
Verma, R.P. and Hansch, C. (2007) Matrix metalloproteinases (MMPs): Chemical-biological
functions and QSARs. Bioorganic & Medicinal Chemistry 15, 2223–2268.
Verma, R.P. and Hansch, C. (2009) Camptothecins: A SAR / QSAR Study. Chemical Reviews 109,
213–235.
Vladu, B., Woynarowski, J.M., Manikumar, G., Wani, M.C., Wall, M.E., von Hoff, D.D. and
Wadkins, R.M. (2000) 7- And 10-substituted camptothecins: dependence of topoisomerase I-
DNA cleavable complex formation and stability on the 7- and 10-substituents. Molecular
Pharmacology 57, 243–251.
Wall, M.E., Wani, M.C., Cook, C.E., Palmer, K.H., McPhail, A.T. and Sim, G.A. (1966) Plant
antitumour agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia
and tumor inhibitor from Camptotheca acuminata. Journal of the American Chemical Society
88, 3888–3890.
Wall, M.E., Wani, M.C., Nicholas, A.W., Manikumar, G., Tele, C., Moore, L., Truesdale, A.,
Leitner, P. and Besterman, J.M. (1993) Plant antitumour agents. 30. Synthesis and structure
activity of novel camptothecin analogs. Journal of Medicinal Chemistry 36, 2689–2700.
Wang, C.-Y., Pan, X.-D., Liu, H.-Y., Fu, Z.-D., Wei, X.-Y. and Yang, L.-X. (2004) Synthesis and
antitumour activity of 20-O-linked nitrogen-based camptothecin ester derivatives. Bioorganic &
Medicinal Chemistry 12, 3657–3662.
Wani, M.C., Nicholas, A.W. and Wall, M.E. (1986) Plant antitumour agents. 23. Synthesis and
antileukemic activity of camptothecin analogs. Journal of Medicinal Chemistry 29, 2358–2363.
Wani, M.C., Nicholas, A.W. and Wall, M.E. (1987b) Plant antitumour agents. 28. Resolution of a key
tricyclic synthon, 5'(RS)-1,5-dioxo-5'-ethyl-5'-hydroxy-2'H,5'H,6'H-6'-oxopyrano[3',4'-f]6,8-
tetrahydroindolizine: total synthesis and antitumour activity of 20(S)- and 20(R)-camptothecin.
Journal of Medicinal Chemistry 30, 2317–2319.
Wani, M.C., Nicholas, A.W., Manikumar, G. and Wall, M.E. (1987a) Plant antitumour agents. 25.
Total synthesis and antileukemic activity of ring A substituted camptothecin analogues.
Structure-activity correlations. Journal of Medicinal Chemistry 30, 1774–1779.
Watase, I., Sudo, H., Yamazaki, M. and Saito, K. (2004) Regeneration of transformed Ophiorrhiza
pumila plants producing camptothecin. Plant Biotechnology 21, 337–342.
Yaegashi, T., Sawada, S., Nagata, H., Furuta, T., Yokokura, T. and Miyasaka, T. (1994) Synthesis
and antitumour activity of 20(S)-camptothecin derivatives. A-ring-substituted 7-
ethylcamptothecins and their E-ring-modified water-soluble derivatives. Chemical &
Pharmaceutical Bulletin 42, 2518–2525.
Yamazaki, Y., Sudo, H., Yamazaki, M., Aimi, N. and Saito, K. (2003) Camptothecin biosynthetic
genes in hairy roots of Ophiorrhiza pumila: Cloning, characterization and differential expression
in tissues and by stress compounds. Plant and Cell Physiology 44, 395–403.
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INDEX
A. caesium
40
A. rhizogenes
19, 124, 149–150, 156–158, 162–164, 183–184, 186–189,
191–192
AAT 39
Acacia nilotica
74, 77, 91
Acanthus illicifolius
73–74
Aconitum napellus
74
ACP 39
adapters 73–74
ADH 39
adjuvant 177, 261, 280–281, 283
adsorption 22, 247, 250–251
AFLP 23–24, 63, 72, 76, 85, 268–269, 272–274
Agrobacterium rhizogenes
19, 122, 149, 156, 181, 183–184, 215, 316, 330
Agrobacterium tumefaciens
293
AIDS 2, 159, 180, 244, 339–340, 342–344
allele 51, 72, 74, 76–80, 82
American Type Culture Collection 122, 184
analysis of genetic variation 64, 268
analytical platforms 23, 222–237
annotation 225, 227–229, 233–234
anthocyanin 5, 20, 163, 167
anthraquinone 20
antibody
monoclonal
6, 21, 281–284, 296
6, 282
anticancer 2, 7, 13, 18, 26, 37, 118, 139, 141, 145, 150–152, 159,
164, 177, 197–198, 211, 244–265, 268, 303–317, 323–
324, 346–347, 354
antigen 277, 279–284, 289–290, 291, 296–298, 338
antigenicity 296
anti-HIV 335, 337–338, 342–343
antiinflammatory 13, 118, 159, 203, 249, 261
antimalarial drug 2, 6
Antirrhinum majus
163
antitumour 1, 9, 145, 259, 326–328, 346–349
antiviral 37, 118, 159, 203, 260, 328, 334–344
apoptosis 254, 303, 311, 313–314, 347
Arabidopsis thaliana
158, 222–226, 229, 237, 295
Aristolochia
86
aromatic ring 304, 323
Artemisia annua
2, 6, 82, 160, 169, 258, 261
artemisinin 2, 6, 13, 16, 159–160, 258, 261–263
aryltetralin lignin 138, 145–146, 331
Aspargus acutifolius
75, 77
Aspargus officinalis
118
Aspergillus
202
Atropa belladonna
2, 6, 23, 168–169
atropine 2, 6, 13
attenuation 213
automated DNA sequencer 7
automation 3, 72
auxin 60–61, 66–67, 107, 149, 157, 190
avidin 14
axenic 186, 190
axillary bud 103, 105, 107, 214
azatoxin 324–326
Bacillus subtilis
289
Bacopa monnieri
118
Berberidaceae 36–37, 48, 138, 140, 145, 199, 267
biodiversity 68, 71, 170
bioinformatics 7–8, 222, 227, 230–231, 244
biolistic 294
biological 2, 7, 37, 100, 108, 115, 118, 125, 152, 165, 181, 198, 203,
211, 222–223, 228, 230–233, 235–236, 244, 246, 249,
252, 263, 304, 311–312, 324, 336, 343, 346–347, 350, 354
biomass 4, 19, 108, 116–117, 123–125, 127, 142, 145, 149, 151,
168–170, 191, 222, 279, 292, 341
bionanostructures 9
biopharmaceuticals 7, 26–28, 227, 278, 296
bioprocess 8, 156
bioprocessing 152, 157, 165, 168
bioreactor 3–7, 9, 14–15, 19, 25, 27, 95, 115, 122–123, 127, 141,
145, 148, 157, 165, 168–170, 190, 218, 330–331, 353
bioremediation 6
biosafety 168, 278
biosynthetic pathways 128, 170, 202, 317, 354
biotech industry 1, 2
biotechnological production 18, 138–152, 316, 330
biotin 74–81
biotransformation 5, 22, 125, 150, 158, 161, 181, 331
Brassica napus
162
Brassica spp
157
breeding
molecular
selection breeding
1, 68, 71, 86, 87, 268, 274
71
94
Butea buteiformis
95
caesin 121
callus induction 42, 59–60
Camellia sinensis
258
Camptotheca acuminata
2, 258–259, 346, 353
camptothecin 2, 13, 18, 26, 159, 246, 254
CaMV 295
cancer 6, 13, 26, 37, 48, 139–141, 145, 159, 177, 179–180, 197,
203, 244, 266, 303–304, 306, 308–310, 312–316, 322,
324, 326–327, 331, 344, 346, 351–353
cannabinoids 98–100, 105, 108–109
Cannabis
71, 73, 75, 77–78, 86, 98–110
Cannabis sativa
73, 98–110
carrier 100, 280–282, 303
catharanthine 21, 157, 164–165, 181–182
Catharanthus roseus
1, 157, 164–165, 170, 176–192, 207
CBRN 2
cDNA 23–24, 163–165, 225, 284, 335, 354
cell lines 17, 19, 22, 25, 123, 127, 149–150, 152, 213, 292, 311,
313, 326, 339, 343, 350, 350
CE-MS 236
Centella asiatica
118–119, 124, 126
centromeric
fingerprinting
308
74, 89, 90, 91, 108, 271, 275, 276
chemical 2, 8, 13, 15–18, 20, 22–23, 43, 49, 62, 98–100, 109, 115,
117–118, 126, 128, 140–141, 144, 160–162, 179, 183,
186, 200, 222, 232, 233, 234, 245, 246–247, 249, 252,
263, 287, 304–305, 312, 321, 323–325, 327, 330, 353
chemotherapy 2, 145, 177, 180, 197, 303, 311, 314
chimeric plant vector 278
Chlamydomonas
293
Chlorella
293
chromatography 100, 187, 230, 335
gas 102, 109
chromosome 48–50, 63–64, 176, 303, 305–306, 308–309, 327
Cinchona ledgeriana
2
Cinchona officinalis
164
Cinchona succirubra
2
Citrus
278
cleavage 284, 287, 326–327, 335
clinical trials 7, 14, 26, 28, 314–315, 327, 347, 354
clone
high yielding
3, 23, 39, 45, 73, 75, 77–83, 103, 109, 128, 183, 186, 190–
191, 213, 216–217, 279, 316, 354
101, 109
cloning 3, 31, 81, 90, 96, 131, 132, 174, 278, 284, 333, 347, 353,
357
CNS stimulant 2, 117–118
co factor 162–163, 166, 234
cocaine 2, 13
co-cultivation 184, 188, 192, 215
colchicine 37, 304, 305, 314, 327
Coleus blumei
4, 9, 20, 21
combinatorial biosynthesis 9
combinatorial chemistry 244, 304
common buck wheat 76, 89 see also Fagopyrum esculentum
conservation of natural resource 2
construct 51, 83, 124, 163–164, 277–280, 282–283
containment 7, 293–294, 296
contamination 3, 158, 168, 288, 292, 341
control 3, 87, 109
Coptis japonica
4, 9, 24
CPMV 282, 294
Crateaegus laevigata
2
cryopreservation 2, 27, 124, 158
cryoprotectant 27
culture
batch
cell
fed batch
media
organ
semi continuous
sub
suspension
tissue
vessels
4–5
4–5, 13–29, 115, 123, 125–127, 138, 141–146, 151–152,
156–157, 163, 165, 168, 198, 201, 203, 213, 289, 292–
293, 295, 298, 316, 329–330, 338
127, 148, 170
200, 293, 343
118–119, 124–125, 142, 152, 197
20
59
24–25, 59, 103, 123–125, 127–128, 141–142, 145, 150,
159, 164, 330, 353
2–3, 14, 16, 27, 39, 41–42, 94, 101, 103, 105, 107–109,
115, 142, 152, 162, 198, 213, 293
124, 209, 312, 328
culture (plant)
callus 42–43, 107, 125, 143, 150, 159, 213, 330
Cymbidium ringspot virus 278
cytokinin 42, 60–61, 67, 105, 107, 147, 214–215
databases
dbEST
PDB
PPDB
SWISS- PROT
84, 165, 222–237, 247, 336
84
245, 253, 262
227–228
227
Datura stramonium
6
de novo
5, 191, 245
decarboxylase 164, 167, 354
demethylation of DNA 190
descriptor 246, 248–250, 252, 263, 265, 350–351
diadzein 2
Dioscorea
19
diversity screening 86
DMSO 125, 306
DNA 8, 9, 12, 23, 46, 48, 50, 63, 64, 70, 72, 73, 74, 75, 84, 87,
88, 89, 90, 91, 108, 111, 113, 114, 131–132, 156, 162,
164, 165, 171, 173, 174, 183, 186, 190, 193, 195, 201,
205, 223, 224, 225, 236, 242, 248, 259, 260, 268, 269,
271, 275, 276, 279, 284, 286, 287, 288, 292, 293, 302,
307, 313, 324, 326, 327, 332, 335, 347, 348, 349, 350,
351, 353, 354, 355, 356, 357
DNA sequencing
automated
9, 73
7
docking 244–253, 255–256, 259, 262, 264, 312
dormancy 53–55, 58, 62, 64–65, 68, 117, 199–200, 330
downstream
extraction
processing
4
15, 22, 27, 115
downstream 4, 5, 15, 22, 27, 100, 115, 126, 286, 311
drug discovery 7, 13, 26, 29, 30, 31, 32, 174, 241, 244, 245, 247, 248,
266, 300, 350
effector cells 280
electrophoresis
capillary
PAGE
paper
233
39
186, 190
elicitation 3–5, 20, 24, 115, 120–123, 125–127, 159, 181, 217
ELISA 283, 337
elite
chemotypes 100
embryogenesis 43, 59–60, 62, 66, 68, 94
endangered 36–39, 42–43, 48, 93, 95, 139, 144, 197, 202, 267–268,
331
endophytic fungi 196–202
Entrophosphora infrequens
354
enveloped viruses 334–335, 338–340, 342–344
epipodophyllotoxin 146, 151, 152, 155, 324, 326, 332
epitope 277
Erythroxylon coca
2
Escherichia coli
16, 146, 151–152, 211, 284, 289, 340, 354
EST databases 9, 165, 225
etoposide 37, 48, 139–141, 144–146, 150–152, 159, 180, 197–198,
203, 268, 323–327, 330–331
ex situ
2–3, 68, 95, 161
exogenous 24, 124, 156, 157, 190
explants 41–42, 59, 103, 105–106, 149, 183–184, 186–190, 192,
214–216, 218, 339
expression 9, 25, 29, 35, 132, 163, 165, 166, 195, 223, 224–227, 237,
241–242, 280, 285, 286, 294
levels 279, 295–297
profiling 9
Fagopyrum esculentum
76, 78, 89
farming 6
FDA 27, 140, 288, 303, 341, 346, 349, 354
feedback inhibition 162–163, 166
fermentation 6, 203, 287–288, 293, 298
FIASCO 75–76, 81–82
Ficus
75, 78–79
flanking 73
primer
sequences
75, 81
284
flavonoid 5, 20, 22, 183, 210, 231, 258–260
flux 5, 181
foreign genes 5, 165, 167, 277
fragmentation 307, 313
FT-IR 232
functional genomics 9, 20, 23–24, 225, 231
Fusarium
200
fusion
oncoprotein
proteins
26, 64, 277–278, 334, 338
149
6, 22, 228, 279, 282–283, 291
Gas chromatography-flame
ionization detection 100, 102, 109
GC-MS 233, 236
Genbank 84, 200
gene 4–6, 8–9, 16–17, 20, 22–25, 53, 58, 63, 76, 86, 100, 124,
126, 128, 149, 151, 156–159, 162–167, 180–181, 183,
202–203, 222–229, 231, 234–237, 268–270, 272, 274,
277–280, 284, 289, 293–294, 306, 309–310, 340, 354
genetic
instability 4
map 71
genetically engineered 9, 163, 347, 353
genistein 2, 260
genomics 9, 20, 23–24, 71, 222, 225, 230–231, 235, 244–245
germplasm 1–2, 38–39, 41, 63, 76–77, 80, 82–83, 86, 103, 105, 107–
108, 218, 273–274
GFP 228, see also green fluorescent protein
ginsenosides 4, 9, 115, 117, 118, 120–122, 125, 126, 129, 131, 132,
133, 135, 174
Glycine max
2, 118
glycosylation 6, 17, 118, 287–289, 292–293, 337
GM crops 27
green
fluorescent protein 284, 286 see also GFP
gold 118
hairy roots 217
house 58, 93, 97, 107, 109, 112, 331, 341
tea 258, 265, 266
growth factors 14, 288
hairy root 5–6, 19, 24, 115, 117, 119, 122–124, 126, 128, 143–144,
148–152, 156–170
haploid 192
healthcare 1, 28, 93
hepatitis B 17, 279–280, 282, 287, 290, 297
herb 36, 75, 117, 138, 207, 258, 261, 305
herbal medicine 1, 13, 71, 93, 298
heterologous 9, 30, 34, 151, 161, 163–166, 203, 279, 284, 289, 295,
298, 316, 354
high throughput screening 17, 244, 250
Himalayan 3, 36, 45, 48–49, 63, 68, 138, 139, 144, 192, 199, 207–
208, 214, 218, 267–268, 270, 274
Mayapple 48, 138–139, 267–268 see also Podophyllum hexandrum
Hippophae rhamnoides
75, 79, 84, 85, 91, 197, 206
HIV 6, 11, 140, 286, 298, 300, 302, 334, 335, 337–345
homologous recombination 294
hormone 6, 14, 19–20, 59, 66, 101, 118, 124, 141, 147, 156–157,
159, 184, 214, 224, 260, 288, 312, 330