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Philipp Arendt, Karel Miettinen, Jacob Pollier, Riet De Rycke, Nico Callewaert, Alain Goossens
Saponins are a structurally diverse family of triterpenes that are widely found as main constituents in many traditional plant-based medicines and often have bioactivities of industrial interest. The heterologous production of triterpene saponins in microbes remains challenging and only limited successful pathway engineering endeavors have been reported. To improve the production capacities of a Saccharomyces cerevisiae saponin production platform, we assessed the effects of several hitherto unexplored gene knockout targets on the heterologous production of triterpenoids...
February 16, 2017: Metabolic Engineering
Liangyun Zhou, Guang Yang, Haifeng Sun, Jinfu Tang, Jian Yang, Yizhan Wang, Thomas Avery Garran, Lanping Guo
This study aims to elucidate the underlying molecular mechanisms of artemisinin accumulation induced by Cd. The effects of different Cd concentrations (0, 20, 60, and 120 μmol/L) on the biosynthesis of Artemisia annua L. were examined. Intermediate and end products were quantified by HPLC-ESI-MS/MS analysis. The expression of key biosynthesis enzymes was also determined by qRT-PCR. The results showed that the application of treatment with 60 and 120 μmol/L Cd for 3 days significantly improved the biosynthesis of artemisinic acid, arteannuin B, and artemisinin...
December 8, 2016: Frontiers of Medicine
Mingxuan Wang, Jiachen Zi, Jianhua Zhu, Shan Chen, Pu Wang, Liyan Song, Rongmin Yu
To investigate the effect of artemisinic acid (AA) on improving the production of terpenoid indole alkaloids (TIAs) of Catharanthus roseus cambial meristematic cells (CMCs), feeding AA to C. roseus CMCs caused 2.35-fold and 2.51-fold increases in the production of vindoline and catharanthine, respectively, compared with those of the untreated CMCs. qRT-PCR experiments showed that AA resulted in a 1.36-8.52 fold increase in the transcript levels of several related genes, including octadecanoid-derivative responsive Catharanthus AP2-domain protein 3 (ORCA3), tryptophan decarboxylase (TDC), strictosidine synthase (STR) and desacetoxyvindoline 4-hydroxylase (D4H)...
June 2016: Natural Product Communications
Bo Wang, Arman Beyraghdar Kashkooli, Adrienne Sallets, Hieng-Ming Ting, Norbert C A de Ruijter, Linda Olofsson, Peter Brodelius, Mathieu Pottier, Marc Boutry, Harro Bouwmeester, Alexander R van der Krol
Our lack of full understanding of transport and sequestration of the heterologous products currently limit metabolic engineering in plants for the production of high value terpenes. For instance, although all genes of the artemisinin/arteannuin B (AN/AB) biosynthesis pathway (AN-PW) from Artemisia annua have been identified, ectopic expression of these genes in Nicotiana benthamiana yielded mostly glycosylated pathway intermediates and only very little free (dihydro)artemisinic acid [(DH)AA]. Here we demonstrate that Lipid Transfer Protein 3 (AaLTP3) and the transporter Pleiotropic Drug Resistance 2 (AaPDR2) from A...
July 12, 2016: Metabolic Engineering
Zongyou Lv, Shu Wang, Fangyuan Zhang, Lingxian Chen, Xiaolong Hao, Qifang Pan, Xueqing Fu, Ling Li, Xiaofen Sun, Kexuan Tang
The NAC (NAM, ATAF and CUC) superfamily is one of the largest plant-specific transcription factor families. NAC transcription factors always play important roles in response to various abiotic stresses. A NAC transcription factor gene AaNAC1 containing a complete open reading frame (ORF) of 864 bp was cloned from Artemisia annua. The expression of AaNAC1 could be induced by dehydration, cold, salicylic acid (SA) and methyl jasmonate (MJ), suggesting that it might be a key regulator of stress signaling pathways in A...
September 2016: Plant & Cell Physiology
Sibo Wang, Melissa J Towler, Pamela J Weathers
Roots of plants with high artemisinin-producing leaves increased leaf production of artemisinin in low-producing plants and vice versa indicating roots are involved in controlling artemisinin biosynthesis in shoots. The anti-malarial sesquiterpene, artemisinin, is produced and stored in glandular trichomes (GLTs) of Artemisia annua. Evidence suggested roots, which produce no significant artemisinin nor precursor compounds, regulate production of artemisinin biosynthesis in the leaves. Using grafting, we studied the relationship between rootstock and scion by measuring GLTs and five artemisinic metabolites (artemisinin, deoxyartemisinin, dihydroartemisinic acid, artemisinic acid, arteannuin B) in scions of ungrafted, self-grafted, and cross-grafted plants among three cultivars: S and 15 both having GLTs with artemisinin at 1...
November 2016: Planta
Nicholas Moore, Nawel Hamza, Benedicte Berke, Anwar Umar
Ethnopharmacology aims to identify new therapeutic agents based on their traditional use. It begins by the identification of disease states, and of the traditional therapies for these, most commonly herbals. Herbals of interest are selected from ethnopharmacological surveys, and tested on experimental models of the diseases of interest. Once the activity of the traditional remedy is demonstrated, including dose-dependence, if possible comparatively to reference medications, the active ingredients can be explored, if possible using bioguided extraction...
January 2017: British Journal of Clinical Pharmacology
Paulina Fuentes, Fei Zhou, Alexander Erban, Daniel Karcher, Joachim Kopka, Ralph Bock
Artemisinin-based therapies are the only effective treatment for malaria, the most devastating disease in human history. To meet the growing demand for artemisinin and make it accessible to the poorest, an inexpensive and rapidly scalable production platform is urgently needed. Here we have developed a new synthetic biology approach, combinatorial supertransformation of transplastomic recipient lines (COSTREL), and applied it to introduce the complete pathway for artemisinic acid, the precursor of artemisinin, into the high-biomass crop tobacco...
2016: ELife
Paskorn Muangphrom, Hikaru Seki, Munenori Suzuki, Aya Komori, Mika Nishiwaki, Ryota Mikawa, Ery Odette Fukushima, Toshiya Muranaka
The production of artemisinin, the most effective antimalarial compound, is limited to Artemisia annua. Enzymes involved in artemisinin biosynthesis include amorpha-4,11-diene synthase (ADS), amorpha-4,11-diene 12-monooxygenase (CYP71AV1) and artemisinic aldehyde Δ(11)13 reductase (DBR2). Although artemisinin and its specific intermediates are not detected in other Artemisia species, we reported previously that CYP71AV1 and DBR2 homologs were expressed in some non-artemisinin-producing Artemisia plants. These homologous enzymes showed similar functions to their counterparts in A...
August 2016: Plant & Cell Physiology
Ritesh Kumar Yadav, Rajender Singh Sangwan, Avadesh K Srivastava, Neelam S Sangwan
Artemisia annua accumulates substantial quantities of unique and highly useful antimalarial sesquiternoid artemisinin and related phytomolecules as well as its characteristic essential oil in its glandular trichomes. The phytomolecules are mainly produced in its leaves and inflorescences. Artemisia annua plants were grown under NaCl salinity (50, 100 and 200 mM) stress conditions imposed throughout the entire life cycle of the plant. Results revealed that specialized metabolites like artemisinin, arteannuin-B, artemisinic acid + dihydroartemisinic acid and essential oil accumulation were positively modulated by NaCl salinity stress...
January 2017: Protoplasma
Wanhong Liu, Huanyan Wang, Yupei Chen, Shunqin Zhu, Min Chen, Xiaozhong Lan, Guoping Chen, Zhihua Liao
Previous publications reported that the artemisinin level was increased in Artemisia annua following a night-frost period. However, the molecular mechanism was not clear. In this study, we found that exogenous jasmonate (JA) effectively enhanced the freezing tolerance of A. annua. The JA biosynthetic genes (LOX1, LOX2, allene oxide cyclase [AOC], and jasmonate resistant 1 [JAR1]) were induced by cold stress, leading to an increase in endogenous JA in cold-treated A. annua. Increased endogenous JA enhanced the expression of three JA-responsive transcription factors, ethylene response factor 1, ethylene response factor 2, and octadecanoid-responsive AP2/ERF, all of which were reported to transcriptionally activate the expression of artemisinin biosynthetic genes, such as amorpha-4,11-diene synthase (ADS), CYP71AV1, DBR2, and aldehyde dehydrogenase 1 (ALDH1)...
March 14, 2016: Biotechnology and Applied Biochemistry
Zongyou Lv, Fangyuan Zhang, Qifang Pan, Xueqing Fu, Weimin Jiang, Qian Shen, Tingxiang Yan, Pu Shi, Xu Lu, Xiaofen Sun, Kexuan Tang
There are many biosynthetic pathways competing for the metabolic flux with the artemisinin biosynthetic pathway in Artemisia annua L. To study the relationship between genes encoding enzymes at branching points and the artemisinin biosynthetic pathway, β-caryophyllene, β-farnesene and squalene were sprayed on young seedlings of A. annua. Transient expression assays indicated that the transcription levels of β-caryophyllene synthase (CPS), β-farnesene synthase (BFS) and squalene synthase (SQS) were inhibited by β-caryophyllene, β-farnesene and squalene, respectively, while expression of some artemisinin biosynthetic pathway genes increased...
March 2016: Plant & Cell Physiology
Talal Waqar, Arshad Khushdil, Khalid Haque
OBJECTIVE: To ascertain the efficacy of chloroquine as first line agent in treatment of uncomplicated malaria -caused by Plasmodium vivax in children---and to determine its current treatment practice in Pakistan. METHODS: This pilot study was conducted at the Paediatrics Department of Combined Military Hospital (CMH), Lahore, Pakistan. Forty-eight children between six months and twelve years of age having positive blood film for Plasmodium vivax were included. They were treated with chloroquine as a drug of - choice...
January 2016: JPMA. the Journal of the Pakistan Medical Association
Frank Sonntag, Cora Kroner, Patrice Lubuta, Rémi Peyraud, Angelika Horst, Markus Buchhaupt, Jens Schrader
Over the last 10 to 15 years, metabolic engineering of microbes has become a versatile tool for high-level de novo synthesis of terpenoids, with the sesquiterpenoids armopha-1,4-diene, farnesene and artemisinic acid as prime examples. However, almost all cell factory approaches towards terpenoids to date have been based on sugar as the raw material, which is mainly used as a food resource and subject to high price volatilities. In this study we present de novo synthesis of the sesquiterpenoid α-humulene from the abundantly available non-food carbon source methanol by metabolically engineered Methylobacterium extorquens AM1...
November 2015: Metabolic Engineering
Jianhua Zhu, Lijia Chen, Xianjing Hu, Liyan Song, Mingxuan Wang, Rongmin Yu
BACKGROUND: The biosynthesis of artemisinin derivatives is one of the interesting subjects. Artemisinic acid (AA) has been widely studied as a supposed intermediate in the biosynthetic pathway leading to artemisinin in Artemisia annua. OBJECTIVE: To investigate the bioconversion of AA by transgenic crown galls of Panax quinquefolium. MATERIALS AND METHODS: AA was administered into crown galls of P. quinquefolium and co-cultured for 2 days...
July 2015: Pharmacognosy Magazine
Hye Kyung Baek, Hyeji Shim, Hyunmook Lim, Minju Shim, Chul-Kyu Kim, Sang-Kyu Park, Yong Seok Lee, Ki-Duk Song, Sung-Jo Kim, Sun Shin Yi
Obesity has increased continuously in western countries during the last several decades and recently become a problem in developing countries. Currently, anti-obesity drugs originating from natural products are being investigated for their potential to overcome adverse effects associated with chemical drugs. Artemisinic acid, which was isolated from the well-known anti-malaria herb Artemisia annua (AA) L., was recently shown to possess anti-adipogenic effects in vitro. However, the anti-adipogenic effects of AA in animal models have not yet been investigated...
2015: Journal of Veterinary Science
Dong-Ming Ma, Zhilong Wang, Liangjiang Wang, Fatima Alejos-Gonzales, Ming-An Sun, De-Yu Xie
Scenarios of genes to metabolites in Artemisia annua remain uninvestigated. Here, we report the use of an integrated approach combining metabolomics, transcriptomics, and gene function analyses to characterize gene-to-terpene and terpene pathway scenarios in a self-pollinating variety of this species. Eighty-eight metabolites including 22 sesquiterpenes (e.g., artemisinin), 26 monoterpenes, two triterpenes, one diterpene and 38 other non-polar metabolites were identified from 14 tissues. These metabolites were differentially produced by leaves and flowers at lower to higher positions...
November 2, 2015: Molecular Plant
Yì-Xiáng J Wáng, Fan Xiao
OBJECTIVE: This survey aims to scrutinize important medical innovations in Chinese mainland since Xinhai (Hsin-hai) revolution in 1911, which marked the end of Manchurian imperial rule and the beginning of China's republican era. METHODS: An online cross-sectional survey was carried out during the period of Dec 29, 2014 to Feb 5, 2015, totaling 37 days. The survey was conducted on the platform provided by DXY (, which is the largest medical and paramedical related website in China...
June 2015: Quantitative Imaging in Medicine and Surgery
Ke Yang, Sajad Rashidi Monfared, Hongzhen Wang, Anneli Lundgren, Peter E Brodelius
No abstract text is available yet for this article.
July 2015: Plant Molecular Biology
Thomas S Kunuanunua, Célestin N Nsibu, Joseph M Bodi, Thérèse K Tshibola, Mimy Makusi Bura, Kumbundu Magoga, Mathilde B Ekila, Hypolite T Situakibanza, Michel N Aloni
The decline of susceptibility of Plasmodium falciparum to chloroquine and sulfadoxine-pyrimethamine resulted in the change of drug policy. This policy has probably changed the facies of the severe form of malaria. A prospective study was conducted in Kinshasa, the Democratic Republic of Congo. Data on children aged ≤13 years, diagnosed with severe malaria were analyzed. In total, 378 children were included with an overall median age of 8 years (age range: 1-13 years). Dark urine was seen in 25.1% of cases...
August 2015: Journal of Tropical Pediatrics
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