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Production of the antimalarial drug precursor artemisinic acid in engineered yeast.
Dae-Kyun Ro1, Eric M Paradise, Mario Ouellet
1California Institute of Quantitative Biomedical Research, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA.
Nature
|April 14, 2006
Summary
Scientists engineered yeast to produce artemisinic acid, a precursor to the antimalarial drug artemisinin. This sustainable microbial production offers a potential solution to artemisinin shortages and high costs, aiding malaria treatment.
Area of Science:
- Biotechnology
- Medicinal Chemistry
- Parasitology
Background:
- Malaria remains a significant global health threat, affecting millions annually.
- Drug-resistant Plasmodium falciparum strains complicate malaria control efforts.
- Artemisinin, a key antimalarial, faces supply shortages and high costs due to extraction and synthesis challenges.
Purpose of the Study:
- To engineer Saccharomyces cerevisiae for cost-effective and sustainable production of artemisinic acid, a precursor to artemisinin.
- To develop a reliable microbial source for artemisinin synthesis, addressing supply limitations.
- To enable simpler purification of artemisinic acid through engineered yeast secretion.
Main Methods:
- Engineered the mevalonate pathway in Saccharomyces cerevisiae.
- Introduced amorphadiene synthase and a novel cytochrome P450 monooxygenase (CYP71AV1) from Artemisia annua.
- Optimized artemisinic acid production and secretion by the engineered yeast.
Main Results:
- Achieved high titres of artemisinic acid (up to 100 mg l(-1)) in engineered yeast.
- Demonstrated that synthesized artemisinic acid is secreted and retained extracellularly, simplifying purification.
- Engineered yeast exhibited higher specific productivity compared to the natural plant source, Artemisia annua.
Conclusions:
- Microbial production of artemisinic acid is feasible and offers a promising alternative to traditional artemisinin sourcing.
- Further optimization and scale-up are necessary for industrial viability and significant cost reduction of artemisinin-based therapies.
- This approach could improve access to essential antimalarial treatments globally.
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