Production of Dictyostelium discoideum Hybrid Type Enzyme SteelyA in the Diatom Phaeodactylum tricornutum

Sene, Nicolas; Lamichhane, Basanta; Gélinas, Sarah-Eve; Custeau, Alexandre; Merindol, Natacha; Meddeb-Mouelhi, Fatma; Desgagné-Penix, Isabel

doi:10.3390/app152111679

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Production of Dictyostelium discoideum Hybrid Type Enzyme SteelyA in the Diatom Phaeodactylum tricornutum

by

Nicolas Sene

,

Basanta Lamichhane

,

Sarah-Eve Gélinas

,

Alexandre Custeau

,

Natacha Merindol

,

Fatma Meddeb-Mouelhi

and

Isabel Desgagné-Penix

^*

Department of Biochemistry, Chemistry, Physics and Forensic Science, Université du Québec à Trois-Rivières, Trois-Rivières, QC G8Z 4M3, Canada

^*

Author to whom correspondence should be addressed.

Appl. Sci. 2025, 15(21), 11679; https://doi.org/10.3390/app152111679 (registering DOI)

Submission received: 16 September 2025 / Revised: 15 October 2025 / Accepted: 22 October 2025 / Published: 31 October 2025

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Abstract

The bioproduction of high-value molecules offers a sustainable and cost-effective alternative to traditional extraction and chemical synthesis, particularly for complex metabolites like cannabinoids (CBs), which have therapeutic potential for neurodegenerative diseases. The marine diatom Phaeodactylum tricornutum presents a promising chassis for CB biosynthesis due to its high lipid content, essential building blocks to biosynthesize CBs. In this study, we explored the feasibility of producing olivetolic acid (OA), the key CB precursor, using a hybrid-type polyketide synthase, SteelyA, from Dictyostelium discoideum. Unlike the native Cannabis sativa enzymes—tetraketide synthase and olivetolic acid cyclase—which exhibit low productivity and stability in diatoms, SteelyA was expected to offer an alternative biosynthetic route. Heterologous production in P. tricornutum resulted in a C-terminal fragment of the SteelyA enzyme, suggesting partial expression or processing of the very high-molecular-weight (352 kDa) SteelyA protein over six months without affecting cellular growth. However, HPLC-MS analysis did not detect intracellular OA or its derivatives in vivo and in vitro, suggesting enzymatic inactivity or metabolic limitations. These negative findings highlight the need for further investigation into the metabolic and proteomic requirements for CB precursor biosynthesis in diatoms, guiding future optimization strategies for sustainable cannabinoid production.

Keywords: metabolic engineering; cannabinoids; cannabinoid precursor; microalgae; diatom bioengineering; heterologous production; high-molecular-weight protein; hybrid polyketide synthase; olivetolic acid; Phaeodactylum tricornutum; secondary metabolite biosynthesis; SteelyA

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MDPI and ACS Style

Sene, N.; Lamichhane, B.; Gélinas, S.-E.; Custeau, A.; Merindol, N.; Meddeb-Mouelhi, F.; Desgagné-Penix, I. Production of Dictyostelium discoideum Hybrid Type Enzyme SteelyA in the Diatom Phaeodactylum tricornutum. Appl. Sci. 2025, 15, 11679. https://doi.org/10.3390/app152111679

AMA Style

Sene N, Lamichhane B, Gélinas S-E, Custeau A, Merindol N, Meddeb-Mouelhi F, Desgagné-Penix I. Production of Dictyostelium discoideum Hybrid Type Enzyme SteelyA in the Diatom Phaeodactylum tricornutum. Applied Sciences. 2025; 15(21):11679. https://doi.org/10.3390/app152111679

Chicago/Turabian Style

Sene, Nicolas, Basanta Lamichhane, Sarah-Eve Gélinas, Alexandre Custeau, Natacha Merindol, Fatma Meddeb-Mouelhi, and Isabel Desgagné-Penix. 2025. "Production of Dictyostelium discoideum Hybrid Type Enzyme SteelyA in the Diatom Phaeodactylum tricornutum" Applied Sciences 15, no. 21: 11679. https://doi.org/10.3390/app152111679

APA Style

Sene, N., Lamichhane, B., Gélinas, S.-E., Custeau, A., Merindol, N., Meddeb-Mouelhi, F., & Desgagné-Penix, I. (2025). Production of Dictyostelium discoideum Hybrid Type Enzyme SteelyA in the Diatom Phaeodactylum tricornutum. Applied Sciences, 15(21), 11679. https://doi.org/10.3390/app152111679

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Production of Dictyostelium discoideum Hybrid Type Enzyme SteelyA in the Diatom Phaeodactylum tricornutum

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