Production of the antimalarial drug precursor artemisinic acid in engineered yeast

@article{Ro2006ProductionOT,
  title={Production of the antimalarial drug precursor artemisinic acid in engineered yeast},
  author={Dae-Kyun Ro and Eric M. Paradise and Mario Ouellet and Karl Fisher and Karyn L. Newman and John M Ndungu and Kimberly A. Ho and Rachel Eachus and Timothy S. Ham and James E Kirby and Michelle C. Y. Chang and Sydnor T. Withers and Y Shiba and Richmond Sarpong and Jay D. Keasling},
  journal={Nature},
  year={2006},
  volume={440},
  pages={940-943}
}
Malaria is a global health problem that threatens 300–500 million people and kills more than one million people annually. Disease control is hampered by the occurrence of multi-drug-resistant strains of the malaria parasite Plasmodium falciparum. Synthetic antimalarial drugs and malarial vaccines are currently being developed, but their efficacy against malaria awaits rigorous clinical testing. Artemisinin, a sesquiterpene lactone endoperoxide extracted from Artemisia annua L (family Asteraceae… 

Continuous-flow synthesis of the anti-malaria drug artemisinin.

Combined with the production of artemisinic acid in engineered yeast, access to the muchneeded malaria drug is now possible by semi-synthesis rather than isolation from plants, ensuring a steady supply of art Artemisinin at greatly reduced cost.

Infectious diseases: New routes to antimalarials?

  • S. Barton
  • Biology, Chemistry
    Nature Reviews Drug Discovery
  • 2006
The genetic engineering of Saccharomyces cerevisiae is described to potentially provide a more facile, cheaper route to artemisinin from the precursor artemisinic acid, which has implications for the development of more affordable treatments for malaria.

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

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 art Artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs.

Generation of the potent anti-malarial drug artemisinin in tobacco

The metabolic engineering of tobacco to produce artemisinin is reported, generating transgenic plants that express five plantand yeast-derived genes involved in the mevalonate and art Artemisinin pathways, all expressed from a single vector, demonstrating that artemis inin can be fully biosynthesized in a heterologous plant system, such as tobacco.

Building a golden triangle for the production and use of artemisinin derivatives against falciparum malaria in Africa

The key genes encoding for enzymes regulating the biosynthesis of artemisinin in planta are fully understood to enable metabolic engineering of the pathway, and results from pilot genetic engineering studies in microbial strains thus far are very inspiring.

Induction of multiple pleiotropic drug resistance genes in yeast engineered to produce an increased level of anti-malarial drug precursor, artemisinic acid

The data presented here suggest that the engineered yeast producing artemisinic acid suffers oxidative and drug-associated stresses, and the use of plant-derived transporters and optimizing AMO activity may improve the yield of artemisic acid production in the genetically engineered yeast.

Recent Advances to Enhance Yield of Artemisinin: A Novel Antimalarial Compound, in Artemisia annua L. Plants

Non-conventional approaches have to be developed to evolve novel strains of the plant to optimize and scale up the production of artemisinin in bulk and make it available to ACT manufacturers at a price much lower than their current cost in turn making an important contribution toward attaining the goals of global malaria eradication programs.

Malaria and artemisinin derivatives: an updated review.

In this review, drugs of choice about malaria i.e. artemisinin and its analogus/derivatives have been discussed in detail e.g. bioavailability, formulation development, stability, combination therapy, additional benefits, drug resistance and toxicity have been reviewed.

Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches

This review analyses the most recent scientific research conducted for the purpose of enhancing artemisinin production to develop better art Artemisinin enhancement strategies which lead to decreased price of ACTs and increased profit to farmers.

Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin

Progress is described toward the goal of developing a supply of semisynthetic artemisinin based on production of the art Artemisinin precursor amorpha-4,11-diene by fermentation from engineered Saccharomyces cerevisiae, and its chemical conversion to dihydroartemisinic acid, which can be subsequently converted to artemis inin.
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