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amorpha fruticosa/抗マラリア剤

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The sesquiterpenoid artemisinin, isolated these from the plant Artemisia annua L., and its semi-synthetic derivatives are a new and very effective group of antimalarial drugs. A branch point in the biosynthesis of this compound is the cyclisation of the ubiquitous precursor farnesyl diphosphate into
The introduction or creation of metabolic pathways in microbial hosts has allowed for the production of complex chemicals of therapeutic and industrial importance. However, these pathways rarely function optimally when first introduced into the host organism and can often deleteriously affect host
Artemisinin-based combination therapies (ACTs) are recommended to be the most effective therapies for the first-line treatment of uncomplicated falciparum malaria. However, artemisinin is often in short supply and unaffordable to most malaria patients, which limits the wide use of ACTs. Production

High-level production of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli.

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BACKGROUND Artemisinin derivatives are the key active ingredients in Artemisinin combination therapies (ACTs), the most effective therapies available for treatment of malaria. Because the raw material is extracted from plants with long growing seasons, artemisinin is often in short supply, and

Over-expression of HMG-CoA reductase and amorpha-4,11-diene synthase genes in Artemisia annua L. and its influence on artemisinin content.

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Artemisinin, an endoperoxide sesquiterpene lactone, is a novel antimalarial natural product isolated from Artemisia annua L. plants. The low concentrations (0.01-1.1%) of this compound in A. annua L. plants is, however, a major constraint for commercialization of artemisinin-based combination
Amorpha-4,11-diene synthase (ADS) of Artemisia annua L. is a sesquiterpene cyclase that catalyzes the conversion of farnesyl diphosphate into amorpha-4,11-diene in the biosynthesis of the antimalarial artemisinin. To explore the mechanisms regulating the tissue-specific and developmental

Systematic identification of functional residues of Artemisia annua amorpha-4,11-diene synthase.

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Terpene synthases (TPSs) are responsible for the extremely diversified and complex structure of terpenoids. Amorpha-4,11-diene synthase (ADS) has a high (90%) fidelity in generating the sesquiterpene precursor for the biosynthesis of artemisinin, an antimalarial drug, however, little is known about

Silencing amorpha-4,11-diene synthase Genes in Artemisia annua Leads to FPP Accumulation.

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Artemisia annua is established as an efficient crop for the production of the anti-malarial compound artemisinin, a sesquiterpene lactone synthesized and stored in Glandular Secretory Trichomes (GSTs) located on the leaves and inflorescences. Amorpha-4,11-diene synthase (AMS) catalyzes the

Comparative functional analysis of CYP71AV1 natural variants reveals an important residue for the successive oxidation of amorpha-4,11-diene.

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Artemisinin is an antimalarial sesquiterpenoid isolated from the aerial parts of the plant Artemisia annua. CYP71AV1, a cytochrome P450 monooxygenase was identified in the artemisinin biosynthetic pathway. CYP71AV1 catalyzes three successive oxidation steps at the C12 position of amorpha-4,11-diene
Artemisinin derivatives are effective anti-malarial drugs. In order to design transgenic plants of Artemisia annua with enhanced biosynthesis of artemisinin, we are studying the promoters of genes encoding enzymes involved in artemisinin biosynthesis. A 1,151 bp promoter region of the cyp71av1 gene,

Catalysis of amorpha-4,11-diene synthase unraveled and improved by mutability landscape guided engineering.

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Amorpha-4,11-diene synthase (ADS) cyclizes the substrate farnesyl pyrophosphate to produce amorpha-4,11-diene as a major product. This is considered the first committed and rate-limiting step in the biosynthesis of the antimalarial artemisinin. Here, we utilize a reported 3D model of ADS to perform

Synthesis of amorpha-4,11-diene from dihydroartemisinic acid.

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Amorphadiene is a natural product involved in the biosynthesis of the antimalarial drug artemisinin. A convenient four-step synthesis of amorphadiene, starting from commercially available dihydroartemisinic acid, is reported. The targeted molecule is isolated with an overall yield of 85% on a

Improvement of amorpha-4,11-diene production by a yeast-conform variant of Vitreoscilla hemoglobin.

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Amorpha-4,11-diene is the precursor of the antimalarial compound artemisinin. The effect of Vitreoscilla hemoglobin (VHb) and its yeast-conform variant (VHbm) on amorpha-4,11-diene production in engineered Saccharomyces cerevisiae was investigated. First, the VHb gene was mutated to the

Combinatorial engineering of mevalonate pathway for improved amorpha-4,11-diene production in budding yeast.

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Combinatorial genome integration of mevalonate pathway genes was performed with the aim of optimizing the metabolic flux for improved production of terpenoids in budding yeast. In the present study, we developed a novel δ-integration platform to achieve multiple genome integrations through

Cyclization mechanism of amorpha-4,11-diene synthase, a key enzyme in artemisinin biosynthesis.

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Cyclization of farnesyl diphosphate into amorpha-4,11-diene by amorpha-4,11-diene synthase (ADS) initiates biosynthesis of artemisinin, a clinically important antimalarial drug precursor. Three possible ring-closure mechanisms, two involving a bisabolyl carbocation intermediate followed by either a
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