Medically Useful Plant Terpenoids: Biosynthesis, Occurrence, and Mechanism of Action

被引:246
作者
Bergman, Matthew E. [1 ]
Davis, Benjamin [1 ]
Phillips, Michael A. [1 ,2 ]
机构
[1] Univ Toronto, Dept Cellular & Syst Biol, Toronto, ON M5S 3G5, Canada
[2] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
isoprenoids; plant natural products; terpenoid biosynthesis; medicinal plants; terpene synthases; cytochrome P450s; METHYLERYTHRITOL PHOSPHATE-PATHWAY; 1-DEOXY-D-XYLULOSE 5-PHOSPHATE REDUCTOISOMERASE; ISOPENTENYL DIPHOSPHATE ISOMERASES; ESSENTIAL OIL COMPOSITION; MEVALONIC ACID PATHWAY; INGENOL MEBUTATE GEL; MOLECULAR-CLONING; ISOPRENOID BIOSYNTHESIS; FUNCTIONAL EXPRESSION; ARABIDOPSIS-THALIANA;
D O I
10.3390/molecules24213961
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Specialized plant terpenoids have found fortuitous uses in medicine due to their evolutionary and biochemical selection for biological activity in animals. However, these highly functionalized natural products are produced through complex biosynthetic pathways for which we have a complete understanding in only a few cases. Here we review some of the most effective and promising plant terpenoids that are currently used in medicine and medical research and provide updates on their biosynthesis, natural occurrence, and mechanism of action in the body. This includes pharmacologically useful plastidic terpenoids such as p-menthane monoterpenoids, cannabinoids, paclitaxel (taxol((R))), and ingenol mebutate which are derived from the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway, as well as cytosolic terpenoids such as thapsigargin and artemisinin produced through the mevalonate (MVA) pathway. We further provide a review of the MEP and MVA precursor pathways which supply the carbon skeletons for the downstream transformations yielding these medically significant natural products.
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页数:23
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共 178 条
[51]   Menthol: a natural analgesic compound [J].
Galeotti, N ;
Mannelli, LD ;
Mazzanti, G ;
Bartolini, A ;
Ghelardini, C .
NEUROSCIENCE LETTERS, 2002, 322 (03) :145-148
[52]   Distinct Autophagosomal-Lysosomal Fusion Mechanism Revealed by Thapsigargin-Induced Autophagy Arrest [J].
Ganley, Ian G. ;
Wong, Pui-Mun ;
Gammoh, Noor ;
Jiang, Xuejun .
MOLECULAR CELL, 2011, 42 (06) :731-743
[53]   METABOLIC COSTS OF TERPENOID ACCUMULATION IN HIGHER-PLANTS [J].
GERSHENZON, J .
JOURNAL OF CHEMICAL ECOLOGY, 1994, 20 (06) :1281-1328
[54]   The function of terpene natural products in the natural world [J].
Gershenzon, Jonathan ;
Dudareva, Natalia .
NATURE CHEMICAL BIOLOGY, 2007, 3 (07) :408-414
[55]   Current perspectives on the mechanism of action of artemisinins [J].
Golenser, Jacob ;
Waknine, Judith H. ;
Krugliak, Miriam ;
Hunt, Nicholas H. ;
Grau, Georges E. .
INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2006, 36 (14) :1427-1441
[56]   The early stages of taxol biosynthesis: An interim report on the synthesis and identification of early pathway metabolites [J].
Guerra-Bubb, Jennifer ;
Croteau, Rodney ;
Williams, Robert M. .
NATURAL PRODUCT REPORTS, 2012, 29 (06) :683-696
[57]  
Gutzeit H, 2014, Plant natural products: Synthesis, biological functions and practical applications
[58]   PEP005, a selective small-molecule activator of protein kinase C, has potent antileukemic activity mediated via the delta isoform of PKC [J].
Hampson, P ;
Chahal, H ;
Khanim, F ;
Hayden, R ;
Mulder, A ;
Assi, LK ;
Bunce, CM ;
Lord, JM .
BLOOD, 2005, 106 (04) :1362-1368
[59]   Artemisinin antimalarials do not inhibit hemozoin formation [J].
Haynes, RK ;
Monti, D ;
Taramelli, D ;
Basilico, N ;
Parapini, S ;
Olliaro, P .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (03) :1175-1175
[60]   Cross-talk between the cytosolic mevalonate and the plastidial methylerythritol phosphate pathways in Tobacco Bright Yellow-2 cells [J].
Hemmerlin, A ;
Hoeffler, JF ;
Meyer, O ;
Tritsch, D ;
Kagan, IA ;
Grosdemange-Billiard, C ;
Rohmer, M ;
Bach, TJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (29) :26666-26676