Mass cultivation of the dinoflagellate Alexandrium pacificum for gonyautoxin-1,4 production

Abstract Bioactive venoms and toxins are emerging as a promising source of drug leads. Optimized through evolution, these compounds display remarkable selectivity and ligand affinity toward a range of relevant pharmacological targets. The successful development of new drugs from toxins is hampered i...

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Main Authors: Hannah Greenhough, Craig Waugh, Roel van Ginkel, Joel Bowater, Gurmeet Kaur, Joy Oakly, Maxence Plouviez, Richard A. Ingebrigtsen, Johan Svenson, Andrew I. Selwood
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-91576-x
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author Hannah Greenhough
Craig Waugh
Roel van Ginkel
Joel Bowater
Gurmeet Kaur
Joy Oakly
Maxence Plouviez
Richard A. Ingebrigtsen
Johan Svenson
Andrew I. Selwood
author_facet Hannah Greenhough
Craig Waugh
Roel van Ginkel
Joel Bowater
Gurmeet Kaur
Joy Oakly
Maxence Plouviez
Richard A. Ingebrigtsen
Johan Svenson
Andrew I. Selwood
author_sort Hannah Greenhough
collection DOAJ
description Abstract Bioactive venoms and toxins are emerging as a promising source of drug leads. Optimized through evolution, these compounds display remarkable selectivity and ligand affinity toward a range of relevant pharmacological targets. The successful development of new drugs from toxins is hampered in some areas by the chemical complexity of the active compounds, which limits the possibility of using chemical synthesis or recombinant strategies for drug lead generation. Marine paralytic shellfish toxins produced by marine microalgae is one such family of compounds. These compounds are highly potent blockers of voltage-gated ion channels, involved in regulating a range of physiological processes and thus versatile targets for drug development. To overcome the supply issue, the current paper describes the development of a scalable production method to generate gram amounts of gonyautoxin-1,4 by mass cultivation of the dinoflagellate Alexandrium pacificum in artificial seawater. By selecting a high-producing strain and running a series of growth optimization experiments, we have scaled up production from 100 mL to 1150 L, with cellular yields of toxin 30 times higher than in a natural bloom. This allows commercial production of gram amounts of these promising compounds, thereby enabling their use in a range of applications beyond the analytical scale.
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spelling doaj-art-89b006a6e4f74fdbb3cb47cf336ee8342025-08-20T01:57:47ZengNature PortfolioScientific Reports2045-23222025-03-0115111310.1038/s41598-025-91576-xMass cultivation of the dinoflagellate Alexandrium pacificum for gonyautoxin-1,4 productionHannah Greenhough0Craig Waugh1Roel van Ginkel2Joel Bowater3Gurmeet Kaur4Joy Oakly5Maxence Plouviez6Richard A. Ingebrigtsen7Johan Svenson8Andrew I. Selwood9Cawthron InstituteCawthron InstituteCawthron InstituteCawthron InstituteCawthron InstituteCawthron InstituteCawthron InstituteCawthron InstituteCawthron InstituteCawthron InstituteAbstract Bioactive venoms and toxins are emerging as a promising source of drug leads. Optimized through evolution, these compounds display remarkable selectivity and ligand affinity toward a range of relevant pharmacological targets. The successful development of new drugs from toxins is hampered in some areas by the chemical complexity of the active compounds, which limits the possibility of using chemical synthesis or recombinant strategies for drug lead generation. Marine paralytic shellfish toxins produced by marine microalgae is one such family of compounds. These compounds are highly potent blockers of voltage-gated ion channels, involved in regulating a range of physiological processes and thus versatile targets for drug development. To overcome the supply issue, the current paper describes the development of a scalable production method to generate gram amounts of gonyautoxin-1,4 by mass cultivation of the dinoflagellate Alexandrium pacificum in artificial seawater. By selecting a high-producing strain and running a series of growth optimization experiments, we have scaled up production from 100 mL to 1150 L, with cellular yields of toxin 30 times higher than in a natural bloom. This allows commercial production of gram amounts of these promising compounds, thereby enabling their use in a range of applications beyond the analytical scale.https://doi.org/10.1038/s41598-025-91576-xGonyautoxin-1,4Alexandrium pacificumToxin productionArtificial seawaterDinoflagellateOptimization
spellingShingle Hannah Greenhough
Craig Waugh
Roel van Ginkel
Joel Bowater
Gurmeet Kaur
Joy Oakly
Maxence Plouviez
Richard A. Ingebrigtsen
Johan Svenson
Andrew I. Selwood
Mass cultivation of the dinoflagellate Alexandrium pacificum for gonyautoxin-1,4 production
Scientific Reports
Gonyautoxin-1,4
Alexandrium pacificum
Toxin production
Artificial seawater
Dinoflagellate
Optimization
title Mass cultivation of the dinoflagellate Alexandrium pacificum for gonyautoxin-1,4 production
title_full Mass cultivation of the dinoflagellate Alexandrium pacificum for gonyautoxin-1,4 production
title_fullStr Mass cultivation of the dinoflagellate Alexandrium pacificum for gonyautoxin-1,4 production
title_full_unstemmed Mass cultivation of the dinoflagellate Alexandrium pacificum for gonyautoxin-1,4 production
title_short Mass cultivation of the dinoflagellate Alexandrium pacificum for gonyautoxin-1,4 production
title_sort mass cultivation of the dinoflagellate alexandrium pacificum for gonyautoxin 1 4 production
topic Gonyautoxin-1,4
Alexandrium pacificum
Toxin production
Artificial seawater
Dinoflagellate
Optimization
url https://doi.org/10.1038/s41598-025-91576-x
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