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Engineering the unicellular alga Phaeodactylum tricornutum for high‐value plant triterpenoid production
Open accessAbstract
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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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Valuable Products from Biotechnology of Microalgae
Pulz, O., & Gross, W. (2004) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-004-1647-x · Cited by 2,132 · cited 1×
“In recent years, the heterokont algae have become increasingly attractive for biotechnology and metabolic engineering applications because of their high lipid content and existing production for aquaculture (Hamilton et al., 2016; Kroth, 2007a; Nrel 1998; Pulz and Gross, 2004; Wikfors and Ohno, 2001).”
High-level semi-synthetic production of the potent antimalarial artemisinin
Paddon, C. J., Westfall, P. J., Pitera, D. J., Benjamin, K., Fisher, K., McPhee, D., Leavell, M. D., Tai, A., Main, A., Eng, D., et al. (2013) · Nature · doi:10.1038/nature12051 · Cited by 2,060
Sheehan, J., Dunahay, T., Benemann, J., & Roessler, P. (1998) · doi:10.2172/15003040 · Cited by 1,753
The Phaeodactylum genome reveals the evolutionary history of diatom genomes
Bowler, C., Allen, A. E., Badger, J. H., Grimwood, J., Jabbari, K., Kuo, A., Maheswari, U., Martens, C., Maumus, F., Otillar, R., et al. (2008) · Nature · doi:10.1038/nature07410 · Cited by 1,719
Production of plant secondary metabolites: a historical perspective
Bourgaud, F., Gravot, A., Milesi, S., & Gontier, É. (2001) · Plant Science · doi:10.1016/s0168-9452(01)00490-3 · Cited by 1,258
Synthetic protein scaffolds provide modular control over metabolic flux
Dueber, J. E., Wu, G. C., Malmirchegini, G. R., Moon, T. S., Petzold, C. J., Ullal, A. V., Prather, K. L. J., & Keasling, J. D. (2009) · Nature Biotechnology · doi:10.1038/nbt.1557 · Cited by 1,242
Molecular activities, biosynthesis and evolution of triterpenoid saponins
Augustin, J. M., Poulsen, V. K., Andersen, S. B., & Bak, S. (2011) · Phytochemistry · doi:10.1016/j.phytochem.2011.01.015 · Cited by 827
Triterpene Biosynthesis in Plants
Thimmappa, R. B., Geisler, K., Louveau, T., O’Maille, P. E., & Osbourn, A. (2014) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-050312-120229 · Cited by 810
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Nguyen, K., Choi, M. S., Seo, S., Song, J.-H., & Jin, E. (2025) · Microbial Cell Factories · doi:10.1186/s12934-025-02874-y · Cited by 2
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Riccio, G., & Lauritano, C. (2022) · Stresses · doi:10.3390/stresses2030022 · Cited by 2
Phytosterol metabolism in plants and algae, time to dive into the unknown
Blary, A., Darnet, S. H., Berna, A., & Schaller, H. (2022) · Advances in botanical research · doi:10.1016/bs.abr.2021.09.006 · Cited by 1
Synthesis of biobased poly(ether-ester) from potentially bioproduced betulin and p-coumaric acid
Guérin, T., Pollet, É., & Avérous, L. (2024) · Materials Today Sustainability · doi:10.1016/j.mtsust.2024.101039 · Cited by 1
Diatoms as producers of fucoxanthin and polyunsaturated fatty acids
Avsiyan, A. L., & Гудвилович, И. Н. (2025) · Učënye zapiski Kazanskogo universiteta. Seriâ Estestvennye nauki/Učënye zapiski Kazanskogo universiteta. Seriâ Estestvennye nauki/Učenye zapiski Kazanskogo gosudarstvennogo universiteta. Seriâ Estestvennye nauki · doi:10.26907/2542-064x.2025.3.399-440 · Cited by 1
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Patwari, P., Pruckner, F., Morelli, L., & Fabris, M. (2026) · ACS Synthetic Biology · doi:10.1021/acssynbio.5c00919 · Cited by 1
Zhu, J., Chen, W., Li, S., Allen, A. E., Xu, X., Wang, X., Jiang, H., & Gong, Y. (2025) · New Phytologist · doi:10.1111/nph.70829 · Cited by 1
Phaeodactylum tricornutum as a Chassis: Insights into Its Potential, Challenges, and Perspectives
Wang, S., Hao, Y., Qiao, T., Zhang, R., Yu, D., Wang, H., Liu, Y., Sun, Y., Xu, D., Song, X., et al. (2026) · Marine Drugs · doi:10.3390/md24020079 · Cited by 2
Cultivation of Osmundea pinnatifida (Hudson) Stackhouse in the Algem® photobioreactor system
Biancacci, C., McDougall, G. J., Day, J., & Stanley, M. S. (2022) · Journal of Applied Phycology · doi:10.1007/s10811-022-02837-5 · Cited by 1
The Application of DNA Transfer Techniques That Have Been Used in Algae
Jayaprada, T., & Wewalwela, J. J. (2023) · Wiley eBooks · doi:10.1002/9781119857839.ch8 · Cited by 1
Biochemical Compounds in Phaeodactylum tricornutum
Sirotiya, V., & Vinayak, V. (2025) · Wiley eBooks · doi:10.1002/9781394174980.ch3 · Cited by 1
Li, X., Lan, C., Li, X., Hu, Z., & Jia, B. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4185482
Abbriano, R. M., George, J., Kahlke, T., Commault, A. S., & Fabris, M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.02.522487
Yun, H.-S., Yoneda, K., Sugasawa, T., Suzuki, I., & Maeda, Y. (2024) · Marine Biotechnology · doi:10.1007/s10126-024-10390-0
Kadalag, N. L., & Prakash, G. (2025) · Algal Research · doi:10.1016/j.algal.2025.104395
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Rahaman, T., Samanta, S., Seth, A., Debnath, B., & Das, S. (2025) · Current Biotechnology · doi:10.2174/0122115501408500251019130934
Mussagy, C. U., Díaz‐Santos, E., & Meléndez‐Martínez, A. J. (2026) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2026.105681
Fantino, E. I., Mérindol, N., Robles, C. G. G., Awwad, F., dos Santos, K. C. G., Rhéaume, K.-L., Goulet, M., Michaud, D., & Desgagné‐Penix, I. (2026) · Algal Research · doi:10.1016/j.algal.2026.104670
Yang, W., Li, S., Li, X., Qiang, X., Liu, X., Wu, S., Xie, X., Gao, S., & Wang, G. (2026) · Aquaculture · doi:10.1016/j.aquaculture.2026.744128
Microbial genomics and metabolic engineering for enhanced remediation
Singh, H., Kumar, D., & Khatri, M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-36656-7.00013-8
Trevisan, N., Zotou, C., Martins, R., John van der, O. O. S. T., Barbosa, M. J., & D’Adamo, S. (2026) · Trends in biotechnology · doi:10.1016/j.tibtech.2026.05.026
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Soni, U., & Vinayak, V. (2026) · Reference series in phytochemistry · doi:10.1007/978-3-031-80866-1_10-1
Advances in engineering microalgae for heterologous terpenoid synthesis: A review
Yuan, Y., Dai, J.-L., Xiao, L., & Jiang, J. (2026) · Biotechnology Advances · doi:10.1016/j.biotechadv.2026.108993
D’Adamo, S., Trevisan, N., Vunderink, I., Südfeld, C., Wijffels, R. H., & Barbosa, M. J. (2025) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.22204228
Self-citationDesigning Microalgal Platforms for the Future of Bio-Based Manufacturing
D’Adamo, S. (2026) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.22202046
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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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