A glandular trichome-specific monoterpene alcohol dehydrogenase from Artemisia annua

Polichuk, Devin R.; Zhang, Yansheng; Reed, Darwin W.; Schmidt, Janice F.; Covello, Patrick S.

doi:10.1016/j.phytochem.2010.04.026

Cited by 39 publications

(32 citation statements)

References 36 publications

(51 reference statements)

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“…6B) and hyperbolic velocity vs. (À)-ipsdienol concentration (Fig. 6D) (Mayoral et al, 2009;Noge et al, 2008;Polichuk et al, 2010;Powell et al, 2000;Slessor et al, 2010), and V max values between 140 and 564 nmol/min/mg (Polichuk et al, 2010). However, values in the literature were calculated using at least partially purified enzyme preparations, whereas we used unpurified samples that contained significant additional protein content.…”

Section: Discussionmentioning

confidence: 99%

Ipsdienol dehydrogenase (IDOLDH): A novel oxidoreductase important for Ips pini pheromone production

Figueroa-Teran¹,

Welch²,

Blomquist³

et al. 2012

Insect Biochemistry and Molecular Biology

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Section: Discussionmentioning

confidence: 99%

Ipsdienol dehydrogenase (IDOLDH): A novel oxidoreductase important for Ips pini pheromone production

Figueroa-Teran¹,

Welch²,

Blomquist³

et al. 2012

Insect Biochemistry and Molecular Biology

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“…Pentane extracts were concentrated to ,30 ml under a stream of nitrogen and either 10 ml ethyl acetate or 10 ml of a mixture of 1:1 N,O-bis-(trimethylsilyl)acetamide (Sigma-Aldrich)/pyridine (Fluka) was added. The remainder of the pentane was carefully removed under a stream of nitrogen and the final 10-ml sample was analysed by gas chromatography-mass spectrometry (GC-MS) 26 .…”

Section: Letter Researchmentioning

confidence: 99%

“…Substrate specificity was determined in 15-min, 600-ml assays using (1)-borneol (Fluka), (2)-borneol (Fluka) and artemisinic, dihydroartemisinic, artemisia 26 , coniferyl (Sigma-Aldrich), and cinnamyl (Sigma-Aldrich) alcohols. ADH1 only showed considerable dehydrogenase activity with artemisinic alcohol and to a lesser extent with dihydroartemisinic alcohol (4.2% relative to artemisinic alcohol; Supplementary Fig.…”

Section: Letter Researchmentioning

confidence: 99%

High-level semi-synthetic production of the potent antimalarial artemisinin

Paddon

Westfall

Pitera

et al. 2013

Nature

1,697

1,237

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In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths 1 . The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plant Artemisia annua. However, the supply of plant-derived artemisinin is unstable, resulting in shortages and price fluctuations, complicating production planning by ACT manufacturers 2 . A stable source of affordable artemisinin is required. Here we use synthetic biology to develop strains of Saccharomyces cerevisiae (baker's yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin. Previous attempts to produce commercially relevant concentrations of artemisinic acid were unsuccessful, allowing production of only 1.6 grams per litre of artemisinic acid 3 . Here we demonstrate the complete biosynthetic pathway, including the discovery of a plant dehydrogenase and a second cytochrome that provide an efficient biosynthetic route to artemisinic acid, with fermentation titres of 25 grams per litre of artemisinic acid. Furthermore, we have developed a practical, efficient and scalable chemical process for the conversion of artemisinic acid to artemisinin using a chemical source of singlet oxygen, thus avoiding the need for specialized photochemical equipment. The strains and processes described here form the basis of a viable industrial process for the production of semi-synthetic artemisinin to stabilize the supply of artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs. Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price.Before the discovery of the enzymes that complete the biosynthetic pathway of artemisinin production (see Supplementary Fig. 1 for a complete overview), several improvements were made to the original amorphadiene-producing strain Y337 (ref. 3). We replaced the MET3 promoter with the copper-regulated CTR3 promoter (Fig. 1a), enabling restriction of ERG9 expression (ERG9 encodes squalene synthase, which catalyses the competing reaction of joining two farnesyl diphosphate moieties to form squalene) by addition of the inexpensive repressor CuSO 4 to the medium rather than the more expensive methionine 4-6 . Strains Y1516 (P CTR3 -ERG9) and Y337 (P MET3 -ERG9) (Supplementary Table 1) both produced similar amounts of amorphadiene ( Supplementary Fig. 2), demonstrating the equivalence of the MET3 and CTR3 promoters for repression of ERG9 expression. We compared the production of amorphadiene from Y337 with the production of artemisinic acid from Y285, a variant of Y337 that also expressed the amorphadiene oxidase CYP71AV1 (a cytochrome P450) and A. annua CPR1 (...

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“…Similar results were also observed for 8-epi-xanthatin (data not shown). A variety of sesquiterpenoids, such as the anti-malarial compound artemisinin and the anti-tumour compound parthenolide, were reported to be biosynthesized in the glandular trichomes [26,27]. We hypothesized that xanthanolide could also be accumulated in a similar location, the glandular trichomes of X. strumarium .…”

Section: Resultsmentioning

confidence: 99%

Identifying Three Ecological Chemotypes of Xanthium strumarium Glandular Trichomes Using a Combined NMR and LC-MS Method

Chen

Hao

et al. 2013

PLoS ONE

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Xanthanolides, as the sesquiterpene lactones, are reportedly the major components for the pharmacological properties of X. strumarium L. species. Phytochemical studies indicated that the glandular structures on the surface of plant tissues would form the primary sites for the accumulation of this class of the compounds. As the interface between plants and their natural enemies, glandular trichomes may vary with respect to which of their chemicals are sequestered against different herbivores in different ecologies. However, to date, no data are available on the chemical characterisation of X. strumarium glandular cells. In this study, the trichome secretions of the X. strumarium species originating from nineteen unique areas across eleven provinces in China, were analysed by HPLC, LC-ESI-MS and NMR. For the first time three distinct chemotypes of X. strumarium glandular trichomes were discovered along with the qualitative and quantitative evaluations of their presence of xanthanolides; these were designated glandular cell Types I, II, and III, respectively. The main xanthanolides in Type I cells were 8-epi-xanthatin and xanthumin while no xanthatin was detected. Xanthatin, 8-epi-xanthatin, and xanthumin dominated in Type II cells with comparable levels of each being present. For Type III cells, significantly higher concentrations of 8-epi-xanthatin or xanthinosin (relative to xanthatin) were detected with xanthinosin only being observed in this type. Further research will focus on understanding the ecological and molecular mechanism causing these chemotype differences in X. strumarium glandular structures.

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A glandular trichome-specific monoterpene alcohol dehydrogenase from Artemisia annua

Cited by 39 publications

References 36 publications

Ipsdienol dehydrogenase (IDOLDH): A novel oxidoreductase important for Ips pini pheromone production

Ipsdienol dehydrogenase (IDOLDH): A novel oxidoreductase important for Ips pini pheromone production

High-level semi-synthetic production of the potent antimalarial artemisinin

Identifying Three Ecological Chemotypes of Xanthium strumarium Glandular Trichomes Using a Combined NMR and LC-MS Method

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