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Co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila
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Co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila
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Co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila
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Journal Article
Co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila
2015
Overview
Camptothecin (CPT) belongs to a group of monoterpenoidindole alkaloids (TIAs) and its derivatives such as irinothecan and topothecan have been widely used worldwide for the treatment of cancer, giving rise to rapidly increasing market demands. Genes from
Catharanthus roseus
encoding strictosidine synthase (STR) and geraniol 10-hydroxylase (G10H), were separately and simultaneously introduced into
Ophiorrhiza pumila
hairy roots. Overexpression of individual
G10H
(G lines) significantly improved CPT production with respect to non-transgenic hairy root cultures (NC line) and single
STR
overexpressing lines (S lines), indicating that
G10H
plays a more important role in stimulating CPT accumulation than
STR
in
O. pumila
. Furthermore, co-overexpression of
G10H
and
STR
genes (SG Lines) caused a 56% increase on the yields of CPT compared to NC line and single gene transgenic lines, showed that simultaneous introduction of
G10H
and
STR
can produce a synergistic effect on CPT biosynthesis in
O. pumila
. The MTT assay results indicated that CPT extracted from different lines showed similar anti-tumor activity, suggesting that transgenic
O. pumila
hairy root lines could be an alternative approach to obtain CPT. To our knowledge, this is the first report on the enhancement of CPT production in
O. pumila
employing a metabolic engineering strategy.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/107
/ 38/77
/ Antineoplastic Agents, Phytogenic - biosynthesis
/ Antineoplastic Agents, Phytogenic - metabolism
/ Antineoplastic Agents, Phytogenic - pharmacology
/ Cancer
/ Carbon-Nitrogen Lyases - genetics
/ Carbon-Nitrogen Lyases - metabolism
/ Cell Survival - drug effects
/ Cytochrome P-450 Enzyme System - genetics
/ Cytochrome P-450 Enzyme System - metabolism
/ Enzymes
/ Genes
/ Humanities and Social Sciences
/ Humans
/ Plants, Genetically Modified
/ Science
