Making artemisinin☆

Covello, Patrick S.

doi:10.1016/j.phytochem.2008.10.001

Cited by 130 publications

(106 citation statements)

References 38 publications

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“…1; Covello et al, 2008). The isopentenyl phosphate (IPP) in AN originates from both the cytosol and plastid arms of the terpenoid biosynthetic pathway (Towler and Weathers, 2007;Schramek et al, 2010).…”

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confidence: 99%

Reproductive Development Modulates Gene Expression and Metabolite Levels with Possible Feedback Inhibition of Artemisinin in Artemisia annua

et al. 2010

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The relationship between the transition to budding and flowering in Artemisia annua and the production of the antimalarial sesquiterpene, artemisinin (AN), the dynamics of artemisinic metabolite changes, AN-related transcriptional changes, and plant and trichome developmental changes were measured. Maximum production of AN occurs during full flower stage within floral tissues, but that changes in the leafy bracts and nonbolt leaves as the plant shifts from budding to full flower. Expression levels of early pathway genes known to be involved in isopentenyl diphosphate and farnesyl diphosphate biosynthesis leading to AN were not immediately positively correlated with either AN or its precursors. However, we found that the later AN pathway genes, amorpha-4,11-diene synthase (ADS) and the cytochrome P450, CYP71AV1 (CYP), were more highly correlated with AN's immediate precursor, dihydroartemisinic acid, within all leaf tissues tested. In addition, leaf trichome formation throughout the developmental phases of the plant also appears to be more complex than originally thought. Trichome changes correlated closely with the levels of AN but not its precursors. Differences were observed in trichome densities that are dependent both on developmental stage (vegetative, budding, and flowering) and on position (upper and lower leaf tissue). AN levels declined significantly as plants matured, as did ADS and CYP transcripts. Spraying leaves with AN or artemisinic acid inhibited CYP transcription; artemisinic acid also inhibited ADS transcription. These data allow us to present a novel model for the differential control of AN biosynthesis as it relates to developmental stage and trichome maturation and collapse.

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Reproductive Development Modulates Gene Expression and Metabolite Levels with Possible Feedback Inhibition of Artemisinin in Artemisia annua

et al. 2010

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“…After establishing the optimal conditions for AS, we used the same DoE principal for amorphadiene synthase (ADS), a sesquiterpene synthase from the plant A. annua that catalyses the conversion of FDP into amorpha‐4,11‐diene (Scheme 2), a key intermediate in the biosynthesis and the chemical synthesis of artemisinin 14. Artemisinin‐based combination therapy (ACT) is the first‐line treatment of malaria recommended by the World Health Organization (WHO) 15.…”

Section: Resultsmentioning

confidence: 99%

Optimising Terpene Synthesis with Flow Biocatalysis

2017

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Sesquiterpenes are an important family of natural products, many of which exhibit important pharmaceutical and agricultural properties. They are biosynthesised from farnesyl diphosphate in sesquiterpene synthase catalysed reactions. Here, we report the development of a highly efficient segmented flow system for the enzyme‐catalysed continuous flow production of sesquiterpenes. Design of experiment (DoE) methods were used to optimise the performance of the flow biocatalysis, and quantitative yields were achieved by using an operationally simple but highly effective segmented flow system.

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“…This is because Covello (2008), Weathers et al (2011) and Alain (2012) stated that secretions of glandular trichomes have been used for their medicinal properties, and in some cases active ingredients have been marketed as drugs. Artemisinin is as esquiterpene lactone produced in glandular trichomes of A. annua are used for the treatment of malaria as an alternative to quinine drugs, which face increasing resistance from emerging strains of the malaria parasite.…”

Section: Resultsmentioning

confidence: 99%

Systematic significance and pharmaceutical potentials of trichomes in accessions of Sesamum indicum L. Pedaliaceae

Zhigila¹,

Sawa²,

Abdul³

2015

J. Med. Plants Res.

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Fresh leaves of twelve accessions of Sesamum indicum were collected after 12 weeks of planting and morphological-histology of trichomes were studied. These features may be used for the delimitation and determination of pharmaceutical potentials of the accessions. These accessions were found to exhibit high degree of heterogeneity in their trichome features. Nine types of trichomes were observed: unicellular, glandular peltate, capitate glandular, long unbranched uniseriate, short unbranched uniseriate, scale, multicellular, multiseriate capitate glandular and branched uniseriate trichomes. Laleduk recorded the highest number (six types), four in accessions Ex-Sudan, Adaw-ting (Improved) and Ex-Gombe 1, three in accessions Ex-Gombe 3, Ex-Gombe 4, Ex-Gombe 5 and Ex-Gombe 6, two in kenana 4, Adaw-wula and Adaw-ting. The most frequent trichome type is short-unbranched uniseriate (76.52%), followed by long-unbranched uniseriate (72.73% and scale (65.11%). The least frequent was multiseriate capitate glandular (11.5%). The density of trichomes varied from accession to accession. Trichome density was the highest in Ex-Gombe 3 (63.2±0.49 mm 2 ) and the lowest was recorded by ExGombe 4 (4.40±0.29 mm 2 ). The high variation in density coupled with the presence of glandular trichomes suggest that all the parts of these accessions probably contain or secrete chemicals that have many uses in the pesticide, pharmaceutical and flavour/fragrance industries and to conserve water. Furthermore, the trichome features varied from accession to accession; hence, are found to be good diagnostic and additional tool in identification as well as nomenclature of the accessions of S. indicum.

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Making artemisinin☆

Cited by 130 publications

References 38 publications

Reproductive Development Modulates Gene Expression and Metabolite Levels with Possible Feedback Inhibition of Artemisinin in Artemisia annua

Reproductive Development Modulates Gene Expression and Metabolite Levels with Possible Feedback Inhibition of Artemisinin in Artemisia annua

Optimising Terpene Synthesis with Flow Biocatalysis

Systematic significance and pharmaceutical potentials of trichomes in accessions of Sesamum indicum L. Pedaliaceae

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