Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development
Abstract
Recent developments in synthetic biology, combined with continued progress in systems biology and metabolic engineering, have enabled the engineering of microorganisms to produce heterologous molecules in a manner that was previously unfeasible. The successful synthesis and recent entry of semi-synthetic artemisinin into commercial production is the first demonstration of the potential of synthetic biology for the development and production of pharmaceutical agents. In this Review, we describe the metabolic engineering and synthetic biology approaches that were used to develop this important antimalarial drug precursor. This not only demonstrates the incredible potential of the available technologies but also illuminates how lessons learned from this work could be applied to the production of other pharmaceutical agents.
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Presently microbial production is at best semi-synthetic, terminating at artemisinic acid (AA), which must then be extracted from culture and chemically converted to artemisinin using photooxidation.
“Presently microbial production is at best semi-synthetic, terminating at artemisinic acid (AA), which must then be extracted from culture and chemically converted to artemisinin using photooxidation (8, 10).”
From <i>Artemisia annua</i> mutant impaired in artemisinin synthesis demonstrates importance of nonenzymatic conversion in terpenoid metabolism (2016) · cites this paper as [8]
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Isoprenoid drugs, biofuels, and Chemicals–Artemisinin, farnesene, and beyond
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Artemisinin Biosynthesis in Non-glandular Trichome Cells of Artemisia annua
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- Authors
- Paddon, C. J., & Keasling, J. D.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Keasling, Jay D.
- ORCID
- Keasling, Jay D.
- Venue
- Nature Reviews Microbiology
- Published
- 2014-04-01
- Volume
- 12
- Issue
- 5
- Pages
- 355-367
- ISSN
- 1740-1526 (ISSN-L)
- 1740-1534
- OpenAlex
- W2006137883
- Cited by
- 675
- References
- 109
- Citations by year
- 2026: 23 · 2025: 47 · 2024: 50 · 2023: 37 · 2022: 52 · 2021: 56 · 2020: 72 · 2019: 59 · 2018: 60 · 2017: 53 · 2016: 87 · 2015: 60 · 2014: 19
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sanofi
- National Research Council Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Keywords
- metabolic engineering, synthetic biology, heterologous production, Escherichia coli, Saccharomyces cerevisiae, antimalarial drugs, pharmaceutical manufacturing
- MeSH terms
- Antimalarials, Biotechnology, Escherichia coli, Genetic Engineering, Plants, Saccharomyces cerevisiae, Drug Design, Artemisinins, Systems Biology, Synthetic Biology, Metabolic Engineering
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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