This study analyzed and predicted following aspects of isopentenyl py- rophosphate isomerases （IPIs） of five north medicinal plants using bioinformatics methods and tools： physical and chemical properties, hydropho...This study analyzed and predicted following aspects of isopentenyl py- rophosphate isomerases （IPIs） of five north medicinal plants using bioinformatics methods and tools： physical and chemical properties, hydrophobicity/hydrophilicity, trans-membrane domain, secondary structure, subcellular localization and so on. The results showed that： there was no notable difference among the physical and chem- ical properties of IPIs of the five north medicinal plants; the IPIs were mainly hy- drophilic; the IPIs were mainly located in chloroplasts by subcellular localization; serine phosphorylation sites were the most; the secondary structures mainly consist- ed of c^-helixes and random coils; no signal peptide existed, indicating that the pro- tein IPI was non-secreted protein; no trans-membrane domain existed; and one functional domain was shown, Le., Nudix Hydrolase Superfamily. This study is of great significance to research on IPI gene functions, deep research on north medic- inal plants, improvement of efficacy of north medicinal plants and rational develop- ment and utilization of medicinal plant resources.展开更多
Artemisinin is highly effective against drug-resistant malarial parasites, which affects nearly half of the global population and kills 〉500 000 people each year. The primary cost of artemisinin is the very expensive...Artemisinin is highly effective against drug-resistant malarial parasites, which affects nearly half of the global population and kills 〉500 000 people each year. The primary cost of artemisinin is the very expensive process used to extract and purify the drug from Artemisia annua. Elimination of this apparently unnecessary step will make this potent antimalarial drug affordable to the global population living in endemic regions. Here we reported the oral delivery of a non-protein drug artemisinin biosynthesized （~0.8 mg/g dry weight） at clinically meaningful levels in tobacco by engineering two metabolic pathways targeted to three different cellular compartments （chloroplast, nucleus, and mitochondria）. The doubly transgenic lines showed a three-fold enhancement of isopentenyl pyrophosphate, and targeting AACPR, DBR2, and CYP71AV1 to chloroplasts resulted in higher expression and an efficient photo-oxidation of di- hydroartemisinic acid to artemisinin. Partially purified extracts from the leaves of transgenic tobacco plants inhibited in vitro growth progression of Plasmodium falciparum-infected red blood cells. Oral feeding of whole intact plant cells bioencapsulating the artemisinin reduced the parasitemia levels in challenged mice in comparison with commercial drug. Such novel synergistic approaches should facilitate low-cost production and delivery of artemisinin and other drugs through metabolic engineering of edible plants.展开更多
基金Supported by Science and Technology Planning Project of Mudanjiang(G2015d1974)Funding Project of Training of Famous Teachers in Mudanjiang Normal University(2014QNGG1805)~~
文摘This study analyzed and predicted following aspects of isopentenyl py- rophosphate isomerases （IPIs） of five north medicinal plants using bioinformatics methods and tools： physical and chemical properties, hydrophobicity/hydrophilicity, trans-membrane domain, secondary structure, subcellular localization and so on. The results showed that： there was no notable difference among the physical and chem- ical properties of IPIs of the five north medicinal plants; the IPIs were mainly hy- drophilic; the IPIs were mainly located in chloroplasts by subcellular localization; serine phosphorylation sites were the most; the secondary structures mainly consist- ed of c^-helixes and random coils; no signal peptide existed, indicating that the pro- tein IPI was non-secreted protein; no trans-membrane domain existed; and one functional domain was shown, Le., Nudix Hydrolase Superfamily. This study is of great significance to research on IPI gene functions, deep research on north medic- inal plants, improvement of efficacy of north medicinal plants and rational develop- ment and utilization of medicinal plant resources.
文摘Artemisinin is highly effective against drug-resistant malarial parasites, which affects nearly half of the global population and kills 〉500 000 people each year. The primary cost of artemisinin is the very expensive process used to extract and purify the drug from Artemisia annua. Elimination of this apparently unnecessary step will make this potent antimalarial drug affordable to the global population living in endemic regions. Here we reported the oral delivery of a non-protein drug artemisinin biosynthesized （~0.8 mg/g dry weight） at clinically meaningful levels in tobacco by engineering two metabolic pathways targeted to three different cellular compartments （chloroplast, nucleus, and mitochondria）. The doubly transgenic lines showed a three-fold enhancement of isopentenyl pyrophosphate, and targeting AACPR, DBR2, and CYP71AV1 to chloroplasts resulted in higher expression and an efficient photo-oxidation of di- hydroartemisinic acid to artemisinin. Partially purified extracts from the leaves of transgenic tobacco plants inhibited in vitro growth progression of Plasmodium falciparum-infected red blood cells. Oral feeding of whole intact plant cells bioencapsulating the artemisinin reduced the parasitemia levels in challenged mice in comparison with commercial drug. Such novel synergistic approaches should facilitate low-cost production and delivery of artemisinin and other drugs through metabolic engineering of edible plants.
