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Engineering the unicellular alga Phaeodactylum tricornutum for high‐value plant triterpenoid production
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Plant triterpenoids constitute a diverse class of organic compounds that play a major role in development, plant defence and environmental interaction. Several triterpenes have demonstrated potential as pharmaceuticals. One example is betulin, which has shown promise as a pharmaceutical precursor for the treatment of certain cancers and HIV. Major challenges for triterpenoid commercialization include their low production levels and their cost-effective purification from the complex mixtures present in their natural hosts. Therefore, attempts to produce these compounds in industrially relevant microbial systems such as bacteria and yeasts have attracted great interest. Here, we report the production of the triterpenes betulin and its precursor lupeol in the photosynthetic diatom Phaeodactylum tricornutum, a unicellular eukaryotic alga. This was achieved by introducing three plant enzymes in the microalga: a Lotus japonicus oxidosqualene cyclase and a Medicago truncatula cytochrome P450 along with its native reductase. The introduction of the L. japonicus oxidosqualene cyclase perturbed the mRNA expression levels of the native mevalonate and sterol biosynthesis pathway. The best performing strains were selected and grown in a 550-L pilot-scale photobioreactor facility. To our knowledge, this is the most extensive pathway engineering undertaken in a diatom and the first time that a sapogenin has been artificially produced in a microalga, demonstrating the feasibility of the photo-bio-production of more complex high-value, metabolites in microalgae.
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“An example of a modern photobioreactor equipped with a multi-parameter monitoring system is the ALGEM ® Labscale Photobioreactor from Algenuity (Bedfordshire, UK). This device enables precise control of light intensity and wavelength as well as real-time monitoring of microalgae growth rates.”
From Multi-Sensing Monitoring of the Microalgae Biomass Cultivation Systems for Biofuels and Added Value Products Synthesis—Challenges and Opportunities (2025) · cites this paper as [255]
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Metadata
- Authors
- D'Adamo, S., Schiano di Visconte, G., Lowe, G., Szaub‐Newton, J., Beacham, T., Landels, A., Allen, M. J., Spicer, A., & Matthijs, M.
- Affiliations
- Eden Laboratory Algenuity Stewartby UK
- Eden Project (GB)
- Plymouth Marine Laboratory (GB)
- Rothamsted Research (GB)
- University of Exeter (GB)
- Corresponding author
- Matthijs, Michiel
- Venue
- Plant Biotechnology Journal
- Publisher
- Wiley
- Published
- 2018-06-19
- Volume
- 17
- Issue
- 1
- Pages
- 75-87
- ISSN
- 1467-7644 (ISSN-L)
- 1467-7652
- PMC
- PMC6330534
- OpenAlex
- W2800109986
- Cited by
- 129
- References
- 96
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 12 · 2023: 19 · 2022: 16 · 2021: 20 · 2020: 14 · 2019: 12 · 2018: 3
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Plant Biotechnology Journal (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Marine Biological Association (acceptedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Funders
- Seventh Framework Programme (FP7/2007‐2013/, 613692)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Algal biology and biofuel production
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Keywords
- Phaeodactylum tricornutum, betulin, lupeol, oxidosqualene cyclase, cytochrome P450, mevalonate pathway, sterol biosynthesis, pathway engineering, microalgae, photobioreactors, high-value metabolites
- MeSH terms
- Lotus, Lupanes, Betulinic Acid, Cytochrome P-450 Enzyme System, Genetic Engineering, Terpenes, Triterpenes, Diatoms, Bioreactors, Intramolecular Transferases, Plants, Genetically Modified, Medicago truncatula, Pentacyclic Triterpenes
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