Preface ........................................................ ix
1. Introduction ................................................. 1
2. Production of terpenes and terpenoids ....................... 11
2.1. Biosynthesis of isoprenoids ............................ 11
2.1.1. Bacteria and algae .............................. 12
2.1.2. Fungi ........................................... 17
2.1.3. Green plants .................................... 18
2.1.4. Insects ......................................... 24
2.1.5. Vertebrates ..................................... 25
2.1.6. Evolution of isoprenoid biosynthesis ............ 26
2.2. Production of terpenoids by different organisms ........ 30
2.2.1. Monoterpenes .................................... 30
2.2.2. Sesquiterpenes and diterpenes ................... 39
2.2.3. Triterpenes, sterols, steroid hormones and
carotenoids ..................................... 49
2.2.4. Complex terpenoids and isoprenoid structures .... 54
3. The origin and evolution of terpenoid messengers ............ 59
3.1. Selection of key enzymes in isoprenoid biosynthesis .... 59
3.1.1. Key enzymes in MAI and MAD routes ............... 60
3.1.2. The development of regulatory mechanisms ........ 69
3.2. Feedback mechanisms .................................... 74
3.2.1. Key enzyme regulation in non-sterologenic
cells ............................................ 74
3.2.2. Key enzyme regulation in sterologenic cells ..... 77
3.3. Other types of feedback regulation ..................... 81
3.3.1. Internal factors affecting feedback
mechanisms ...................................... 81
3.3.2. External factors affecting feedback
mechanisms ...................................... 83
3.4. Site of action of the regulatory mechanisms ............ 86
3.4.1. Transcriptional and post-transcriptional
regulation ...................................... 86
3.4.2. Oxysterols ...................................... 91
3.4.3 Non-sterol terpenoids ............................ 94
3.5. Interference with DNA synthesis: prenylated proteins ... 96
3.5.1. The mechanism of prenylation .................... 97
3.5.2. Prenylation of Ras proteins .................... 102
3.5.3. Inhibition of protein prenylation .............. 105
4. Specific properties of terpenoids .......................... 109
4.1. Messengers on the cellular level ...................... 109
4.1.1. Messengers within a cell ....................... 110
4.1.2. Messengers within organisms .................... 113
4.1.3. Homeostasis of cell numbers 129
4.1.4. Effects of terpenoids on Ras proteins .......... 135
4.1.5. Cancer research ................................ 141
4.1.6. "To kill or cure, ..." ......................... 153
4.1.7. Terpenoids with different effects on cancer
cells .......................................... 160
4.1.8. Impairment of mevalonic acid synthesis in
tumours ........................................ 166
4.1.9. Terpenoids with unexpected effects ............. 168
4.2. Direct toxic effects .................................. 171
4.2.1. Anti-microbial effects ......................... 171
4.2.2. Toxic effects on insects and other animals ..... 176
4.2.3. How to overcome autotoxicity ................... 178
5. Functions of natural terpenoids in the
interrelationships between organisms ....................... 181
5.1. Semiochemicals ........................................ 182
5.1.1. Sex pheromones and other semiochemicals
with impact on behaviour ....................... 183
5.1.2. Alarm pheromones and defensive secretions ...... 191
5.1.3. Repellents and deterrents: defensive
metabolites by plants .......................... 197
5.1.4. Kairomones ..................................... 216
5.1.5. Synomones ...................................... 222
5.2. Relationship between structure and function ........... 228
5.2.1. Similarities between receptors ................. 228
5.2.2. The role of terpenoids in the evolution of
insect behaviour ............................... 233
5.2.3. Signal transduction and neurological
adaptation ..................................... 243
6. Terpenoids in practice ..................................... 253
6.1. Natural terpenoids and their sources .................. 253
6.1.1. Terpenoids in land plants and simple
isolation procedures ........................... 253
6.1.2. More complex isolation techniques .............. 264
6.2. Utilization of terpenoids in biology and
agriculture ........................................... 269
6.2.1. Beneficial insects ............................. 270
6.2.2. Insect control ................................. 272
6.2.3. Resistance breeding ............................ 286
6.2.4. Other applications ............................. 290
7. Natural terpenoids to the benefit of human health .......... 297
7.1. Applications in medicine .............................. 297
7.1.1. Anti-microbials ................................ 298
7.1.2. Analgesics ..................................... 299
7.1.3. Cholesterolemia, vascular problems, PVD ........ 300
7.1.4. Tracheal and bronchial disorders (COPD) ........ 304
7.1.5. Arthritis, rheumatism, inflammatory
disorders ...................................... 306
7.1.6. Intestinal disorders ........................... 307
7.1.7. Stress-related problems, sedatives ............. 308
7.1.8. Cancer therapies ............................... 309
7.2. Cosmetics ............................................. 329
7.2.1. Sex attractants ................................ 329
7.2.2. Dermatological preparations .................... 331
7.3. Terpenoid analogues and derivatives ................... 333
7.3.1. Applications in agriculture .................... 333
7.3.2. Applications in medicine ....................... 335
8. Prospectus and suggestions for further research ............ 339
8.1. Search for new bioactive terpenoids 339
8.1.1. Incorporation of terpenoids into new
methodologies .................................. 340
8.1.2. Future of terpenoids in registration
requirements ................................... 345
8.2. A multidisciplinary approach .......................... 348
8.2.1 Bacteria, fungi, plants, insects and humans ..... 348
8.2.2 Terpenoids and model systems .................... 351
Epilogue ...................................................... 357
References .................................................... 361
General reading ............................................... 417
Glossary ...................................................... 421
Index ......................................................... 425
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