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SYSTEMATIC NAME
IUBMB Comments
artemisinic aldehyde:NADP+ oxidoreductase
Cloned from Artemisia annua. In addition to the reduction of artemisinic aldehyde it is also able to a lesser extent to reduce artemisinic alcohol and artemisinic acid. Part of the biosyntheis of artemisinin.
artemisinic aldehyde 11 (13) reductase (DBR2) is the checkpoint enzyme catalyzing artemisinic aldehyde to form dihydroartemisinic aldehyde directly involved in artemisinin biosynthetic pathway
the early steps in artemisinin biosynthesis involve amorpha-4,11-diene hydroxylation to artemisinic alcohol, followed by oxidation to artemisinic aldehyde, reduction of the C11-C13 double bond to dihydroartemisinic aldehyde and oxidation to dihydroartemisinic acid
the enzyme plays an important role in the biosynthesis of the antimalarial artemisinin in Artemisia annua. The high artemisin producing plant varieties 2/39, Chongqing, and Anamed produce more artemisinin than arteannuin B, while the low artemisin producing plant varieties Meise, Iran#8, Iran#14, Iran#24, and Iran#47 produce more arteannuin B than artemisinin
presence of a number of biosynthetic enzymes such as the amorpha-4,11-diene synthase and the amorpha-4,11-diene hydroxylase as well as artemisinic alcohol and dihydroartemisinic aldehyde dehydrogenase activities in both leaves and glandular trichomes
glandular trichome, presence of a number of biosynthetic enzymes such as the amorpha-4,11-diene synthase and the amorpha-4,11-diene hydroxylase as well as artemisinic alcohol and dihydroartemisinic aldehyde dehydrogenase activities in both leaves and glandular trichomes
gene DBR2, cloning, sequencing, and analysis of the promoter of the DBR2 gene, detailed overview. The activity of the artemisinic aldehyde DELTA11(13) reductase promoter is important for artemisinin yield in different chemotypes of Artemisia annua, quantitative real-time PCR expression analysis, overview
gene DBR2, overexpression in Artemisia annua under control of the CaMV 35S promoter via transfecton through Agrobacterium tumefaciens strain LBA4404 mediated leaf disc transformation, quantitative real-time PCR expression analysis, method evaluation
gene DBR2, recombinant expression of the enzyme in transgenic Nicotiana tabacum plant leaf chloroplasts via transfection with Agrobacterium tumefaciens strain EHA105, nuclear genome transformation of homoplastomic plant
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression levels of farnesyl diphosphate synthase (FPS), cytochrome P450-dependent hydroxylase CYP71AV1, and double bond reductase 2 (DBR2) are increased significantly in plants overexpressing Artemisia annua allene oxide cyclase, AaAOC. The product of AOC is jasmonate, that induces the expression of FPS, CYP71AV1, and DBR2
the enzyme DBR2 is induced by 0.12 mmol/l of cadmium. Appropriate doses of cadmium can increase the concentrations of artemisinic metabolites at a certain time point by upregulating the relative expression levels of key enzyme genes involved in artemisinin biosynthesis, overview
three jasmonate-responsive transcription factors, ethylene response factor 1, ethylene response factor 2, and octadecanoidresponsive AP2/ERF, all transcriptionally activate the expression of artemisinin biosynthetic genes, such as amorpha-4,11-diene synthase (ADS), CYP71AV1, DBR2, and aldehyde dehydrogenase 1 (ALDH1). Cold stress indirectly activates the DBR2 expression by increasing the amount of jasmonate through upregulation of jasmonate biosynthetic genes (LOX1, LOX2, allene oxide cyclase [AOC], and jasmonate resistant 1 [JAR1]). Levels of artemisinin and related secondary metabolites, such as dihydroartemisinic acid, artemisinin B, and artemisinic acid, are increased in Artemisia annua under cold stress
heterologous expression of Artemisia annua amorphadiene synthase and CYP71AV1, the cytochrome P450 responsible for oxidation of amorphadiene, in tobacco lead to the accumulation of amorphadiene and artemisinic alcohol, but not artemisinic acid, in leaf. Additional expression of artemisinic aldehyde DELTA11(13) double-bond reductase with or without aldehyde dehydrogenase 1 leads to the additional accumulation dihydroartemisinic alcohol
the yield of artemisinin from Artemisia annua is relatively low when cultivated under Indian climatic conditions. Artemisinin biosynthesized at clinically meaningful levels in Nicotiana tabacum by engineering two metabolic pathways targeted to three different cellular compartments (chloroplast, nucleus, and mitochondria). The doubly transgenic lines show a 3fold enhancement of isopentenyl diphosphate, and targeting AACPR, DBR2, and CYP71AV1 to chloroplasts results in higher expression and an efficient photooxidation of dihydroartemisinic acid to artemisinin. Partially purified extracts from the leaves of transgenic Nicotiana tabacum plants inhibit in vitro growth progression of Plasmodium falciparum-infected red blood cells, parasitemia is observed in mice fed with pure artemisinin as well as those fed with the wild-type plant extract, Plasmodium berghei murine malaria model. Artemisinin biosynthesis by sequential metabolic engineering of chloroplast and nuclear genomes, overview
branch pathway blocking in Artemisia annua is a useful method for obtaining high yield artemisinin. In anti-squalene synthase (SQS) transgenic plants, the transcription levels of beta-caryophyllene synthase (CPS), beta-farnesene synthase (BFS), germacrene A synthase (GAS), amorpha-4,11-diene synthase (ADS), amorphadiene 12-hydroxylase (CYP71AV1) and aldehyde dehydrogenase 1 (ALDH1) all increase. Contents of artemisinin and dihydroartemisinic acid are enhanced by 71% and 223%, respectively, while beta-farnesene is raised to 123% compared to control. The mRNA level of artemisinic aldehyde DELTA11(13) reductase (DBR2) does negligibly change in almost all transgenic plants, overview
oral feeding of whole intact plant cells bioencapsulating the artemisinin reduces the Plasmodium falciparum parasitemia levels in challenged mice in comparison with commercial drug. The synergistic approache may facilitate low-cost production and delivery of artemisinin and other drugs through metabolic engineering of edible plants
artemisinin is the main ingredient for malaria prevention. The World Health Organization recommends artemisinin combination therapies (ACT) as the first-line therapy for malaria worldwide
production of artemisin by incubating a mixture of artemisin precursors from engineered Saccharomyces cerevisiae with a cell-free extract of Artemisia annua. Use of cold-acclimated Artemisia annua cell-free extract gives rise to considerable artemisin content up to 0.65%
for enhanced artemisin production, Appropriate doses of Cd can increase the concentrations of artemisinic metabolites at a certain time point by upregulating the relative expression levels of key enzyme genes involved in artemisinin biosynthesis
The molecular cloning of artemisinic aldehyde DELTA11(13) reductase and its role in glandular trichome-dependent biosynthesis of artemisinin in Artemisia annua
Bertea, C.; Freije, J.; Van Der Woude, H.; Verstappen, F.; Perk, L.; Marquez, V.; De Kraker, J.; Posthumus, M.; Jansen, B.; De Groot, A.; Franssen, M.; Bouwmeester, H.
Identification of intermediates and enzymes involved in the early steps of artemisinin biosynthesis in Artemisia annua
Yuan, Y.; Liu, W.; Zhang, Q.; Xiang, L.; Liu, X.; Chen, M.; Lin, Z.; Wang, Q.; Liao, Z.
Overexpression of artemisinic aldehyde DELTA11(13) reductase gene - enhanced artemisinin and its relative metabolite biosynthesis in transgenic Artemisia annua L