Production of dictyostelium discoideum hybrid type enzyme SteelyA in the diatom phaeodactylum tricornutum

Sene, N., Lamichhane, B., Gélinas, S.-E., Custeau, A., Merindol, N., Meddeb-Mouelhi, F. et Desgagné-Penix, I. (2025). Production of dictyostelium discoideum hybrid type enzyme SteelyA in the diatom phaeodactylum tricornutum. Applied Sciences, 15 (21). Article 11679. ISSN 2076-3417 DOI 10.3390/app152111679

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Résumé

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.

Type de document:	Article
Mots-clés libres:	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
Date de dépôt:	07 janv. 2026 16:53
Dernière modification:	07 janv. 2026 16:53
Version du document déposé:	Version officielle de l'éditeur
URI:	https://depot-e.uqtr.ca/id/eprint/12518

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