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
[101]  
Mechoulam R., 1986, PHARMACOHISTORY CANN
[102]   Molecular cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. [J].
Mercke, P ;
Bengtsson, M ;
Bouwmeester, HJ ;
Posthumus, MA ;
Brodelius, PE .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2000, 381 (02) :173-180
[103]   Artemisinin: mechanisms of action, resistance and toxicity [J].
Meshnick, SR .
INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2002, 32 (13) :1655-1660
[104]   Artemisinin and the antimalarial endoperoxides: From herbal remedy to targeted chemotherapy [J].
Meshnick, SR ;
Taylor, TE ;
Kamchonwongpaisan, S .
MICROBIOLOGICAL REVIEWS, 1996, 60 (02) :301-+
[105]   Plant Defense Against Herbivores: Chemical Aspects [J].
Mithoefer, Axel ;
Boland, Wilhelm .
ANNUAL REVIEW OF PLANT BIOLOGY, VOL 63, 2012, 63 :431-450
[106]   Dynamic Metabolons [J].
Moller, Birger Lindberg .
SCIENCE, 2010, 330 (6009) :1328-1329
[107]   Isoprenoid biosynthesis in plants: Carbon partitioning within the cytoplasmic pathway [J].
Newman, JD ;
Chappell, J .
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1999, 34 (02) :95-106
[108]   Biochemical Conservation and Evolution of Germacrene A Oxidase in Asteraceae [J].
Nguyen, Don Trinh ;
Goepfert, Jens Christian ;
Ikezawa, Nobuhiro ;
MacNevin, Gillian ;
Kathiresan, Meena ;
Conrad, Juergen ;
Spring, Otmar ;
Ro, Dae-Kyun .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (22) :16588-16598
[109]   PHORBOL DIESTER RECEPTOR CO-PURIFIES WITH PROTEIN KINASE-C [J].
NIEDEL, JE ;
KUHN, LJ ;
VANDENBARK, GR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (01) :36-40
[110]   Artemisinin-based combination treatment of falciparum malaria [J].
Nosten, Francois ;
White, Nicholas J. .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2007, 77 (06) :181-192