Browsing by Author "Woolley, J. G."
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Item Metadata only Biosynthesis of podophyllotoxin in Linum album cell cultures(Springer, 2002) Seidel, V.; Windhövel, J.; Eaton, G.; Alfermann, A. W.; Arroo, R. R. J.; Medarde, M.; Petersen, M.; Woolley, J. G.Item Metadata only Developing an alternative UK industrial crop Artemisia annua, for the extraction of artemisinin to treat multi-drug resistant malaria.(The Association of Applied Biologists, 2010) Smith, L. M. J.; Bentley, S.; Jones, H.; Burns, C.; Arroo, R. R. J.; Woolley, J. G.Over the last 5 years, new Artemisia annua lines have been produced with increased artemisinin levels, where the artemisinin yield (expressed as percentage artemisinin, by weight in harvested dried leaves) increased from 1.2-2.2%. In addition to these genetic improvements, agronomic techniques that improve the overall yield of artemisinin and increase seed yield have also been achieved. Techniques for accurate measurement of artemisinin have been considered and the presence of additional compounds, which could impact on accurate measurement of the active pharmaceutical ingredient. The genetic and agronomic improvements reported here suggest that artemisinin yields in commercial production could be raised to 60 kg ha-1, a figure that compares well with the 2010 industry average of 24 kg ha-1.Item Open Access Developing Artemisia annua for the extraction of artemisinin to treat multi-drug resistant malaria(National Academy of Sciences of Belarus, 2016-09) Arroo, R. R. J.; Atkinson, C. J.; Bentley, S.; Burns, C.; Davies, M. J.; Dungey, N.; Flockhart, I.; Hill, C.; Robinson, T.; Smith, L. M. J.; Woolley, J. G.Semi-synthetic derivatives of the sesquiterpene artemisinin have worldwide become the main treatment for P. falciparum malaria. Artemisinin-combination therapies (ACTs), containing artemether or artesunate combined with non-isoprenoid drugs, are recommended as first line treatment by the World Health Organization, particularly in areas where resistance against quinine and quinine analogues has developed. Whereas methods for the total synthesis of artemisinin have been developed, artemisinin extracted from the leaves of Artemisia annua L. (Asteraceae) is still the preferred source for commercial production of antimalarial drugs. The biosynthetic pathway of artemisinin is well-known and a number of genes that regulate artemisinin biosynthesis have been identified. Various attempts have been made to enhance the yield of artemisinin in crops or plant cell cultures through the use of genetic engineering. Another approach has been semi-synthesis of artemisinin via artemisinic acid in genetically engineered yeast. Although genetic engineering holds a great promise for the future, currently the largest improvements in artemisinin yield have been obtained through creation of high-yielding varieties by classical breeding programs combined with modern agricultural production techniques.Item Metadata only Enhancement of artemisinin concentration and yield in response to optimization of nitrogen and potassium supply to Artemisia annua.(Oxford University Press, 2009-05-30) Davies, M. J.; Atkinson, C. J.; Burns, C.; Woolley, J. G.; Hipps, N. A.; Arroo, R. R. J.; Dungey, N.; Robinson, T.; Brown, P.; Flockhart, I.; Hill, C.; Smith, Lydia; Bentley, S.Background and Aims: The resurgence of malaria, particularly in the developing world, is considerable and exacerbated by the development of single-gene multi-drug resistances to chemicals such as chloroquinone. Drug therapies, as recommended by the World Health Organization, now include the use of antimalarial compounds derived from Artemisia annua – in particular, the use of artemisinin-based ingredients. Despite our limited knowledge of its mode of action or biosynthesis there is a need to secure a supply and enhance yields of artemisinin. The present study aims to determine how plant biomass can be enhanced while maximizing artemisinin concentration by understanding the plant's nutritional requirements for nitrogen and potassium. Methods: Experiments were carried out, the first with differing concentrations of nitrogen, at 6, 31, 56, 106, 206 or 306 mg L–1 being applied, while the other differing in potassium concentration (51, 153 or 301 mg L–1). Nutrients were supplied in irrigation water to plants in pots and after a growth period biomass production and leaf artemisinin concentration were measured. These data were used to determine optimal nutrient requirements for artemisinin yield. Key Results: Nitrogen nutrition enhanced plant nitrogen concentration and biomass production successively up to 106 mg N L–1 for biomass and 206 mg N L–1 for leaf nitrogen; further increases in nitrogen had no influence. Artemisinin concentration in dried leaf material, measured by HPLC mass spectroscopy, was maximal at a nitrogen application of 106 mg L–1, but declined at higher concentrations. Increasing potassium application from 51 to 153 mg L–1 increased total plant biomass, but not at higher applications. Potassium application enhanced leaf potassium concentration, but there was no effect on leaf artemisinin concentration or leaf artemisinin yield. Conclusions: Artemisinin concentration declined beyond an optimal point with increasing plant nitrogen concentration. Maximization of artemisinin yield (amount per plant) requires optimization of plant biomass via control of nitrogen nutrition.Item Metadata only Hairy root cultures of Datura stramonium: in vovo and in vitro synthesis of tropane alkaloids(1991) Burbridge, A.; Gartland, K. M. A.; Jenkins, R. O.; Woolley, J. G.; Elliott, Malcolm C.Item Metadata only Increases in leaf artemisinin concentration in Artemisia annua in response to the application of phosphorus and boron.(Elsevier, 2011) Davies, M. J.; Atkinson, C. J.; Burns, C.; Arroo, R. R. J.; Woolley, J. G.Malaria resurgence particularly in the third world is considerable and exacerbated by the development of multi-drug resistances to chemicals such as chloroquinone. Drug therapies, as recommended by WHO include the use of antimalarial compounds derived from Artemisia annua L, i.e. artemisinin-based therapies. This work aims to determine how A. annua plant dry matter can be enhanced while maximising artemisinin concentration from understanding the plant's mineral requirements for P and B. Experiments with differing of P, from 5 to 120 mg L(-1) and B from 0.1 to 0.9 mg L(-1) were undertaken. Mineral nutrients were supplied in irrigation water to potted plants and after a period of growth, dry matter production and leaf artemisinin concentration were determined. Increases in P application enhanced plant growth and total dry matter production. An optimal application rate, with respect to dry matter, was apparent around 30 mg P L(-1). Despite increases in P application having no influence on leaf artemisinin concentration, optimal yields of artemisinin, on a per plant basis, were again achieved at supply rate around 30-60 mg L(-1). Increasing B application rate had little influence on dry matter production despite increases in B leaf tissue concentration promoting the total amount of B per plant. Leaf artemisinin concentration significantly increased with B application rate up to 0.6 mg B L(-1). The higher artemisinin concentrations when multiplied by total leaf dry matter at the higher B application rates produced an increase in total artemisinin production per plant. There was however no further significant effect on leaf artemisinin concentration when B supply concentrations increased further (0.9 mg L(-1)). Artemisinin production varied between the two experiments to a greater extent than plant dry matter production and the reasons for this are discussed in relation to growing environments and their possible impacts on artemisinin biosynthesis.Item Metadata only Plant cell factories as a source for anti-cancer lignans(Springer, 2002) Arroo, R. R. J.; Alfermann, A. W.; Medarde, M.; Petersen, M.; Pras, N.; Woolley, J. G.Item Metadata only Screening a diverse collection of Artemisia annua germplasm accessions for the antimalarial compound, artemisinin.(Cambridge University Press, 2012) Cockram, J.; Hill, C.; Burns, C.; Flockhart, I.; Robinson, T.; Dungey, N.; Bentley, S.; Arroo, R. R. J.; Woolley, J. G.; Atkinson, C. J.; Davies, M. J.; Greenland, A. J.; Smith, L. M. J.The antimalarial drug artemisinin (ART) is commercially extracted from the medicinal plant Artemisia annua L. Here, we report the screening of 70 A. annua plants representing 14 diverse germplasm accessions sourced from around the world, and identify lines containing >2% ART. These extremely high-yielding individuals have been maintained as vegetative clones, and they represent promising germplasm resources for future A. annua breeding programmes.Item Metadata only Tropane alkaloid containing plants – Henbane, belladonna, Datura and Duboisia.(Springer, 2007) Arroo, R. R. J.; Woolley, J. G.; Oksman-Caldentey, K. M.