Biological and chemical analysis of azaspiracids and amphidinols originating from dinoflagellate strains associated to Irish waters
Murphy, Elliot Charles
Murphy, Elliot Charles
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Publication Date
2024-04-15
Type
Thesis
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Abstract
Microalgae have the potential to produce biologically active metabolites which can be toxic, affect our fisheries and endanger food safety. Due to their active nature these toxins can also have therapeutic benefits when their toxicity is modulated, or dosage is controlled. Shellfish contamination with azaspiracids (AZAs) is a major and recurrent problem for the Irish shellfish industry. Amphidoma languida, a small thecate dinoflagellate of the family Amphidomataceae which is widely distributed in Irish coastal waters, is one of the identified source species of azaspiracids. Irish and North Sea strains of Am. languida have been found to produce as major metabolites AZA-38 and -39 whose structures have only been provisionally elucidated by mass spectrometry and their toxic potential is currently unknown. Am. languida became the initial focus of this PhD. Bulk culturing of a North Sea strain in a continuous process allowed for the production of over 700 litres of culture. From the biomass produced we were able to isolate the major compound, AZA-39 and elucidate its structure. A mussel feeding study was also performed with live algal cells resulting in the identification of 8 new shellfish metabolites formed from the metabolism of AZA-38 and -39. Furthermore, biotoxin data from the Irish monitoring program identified AZA-38 and -39 in several shellfish species from analysis of routine samples from several locations around Ireland. Although infamous for their toxicity, microalgae have received growing interest for their capacity to produce metabolites with the potential to be therapeutics. The second section in this study on marine dinoflagellates aimed at characterising the antimicrobial potential of the marine dinoflagellate Amphidinium carterae strain LACW11, isolated from the west of Ireland. Amphidinolides (AMs) have been identified as cytotoxic polyoxygenated polyketides produced by several Amphidinium species. Fractions of a A. carterae extract yielded minimum inhibitory concentrations between 16 μg mL−1 and 256 μg mL−1 for both Gram-positive bacteria. A targeted analysis using UHPLC-HRMS applied to fractions G to J evidenced the presence of AM type compounds AM-A, AM-B, AM-22 and a new derivative of AM-A. Combining the results of the biological assays with the chemical analysis of the fractions, we could conclude that AM-A and the dehydrated derivative of AM-A are responsible for the detected antimicrobial bioactivity. A bulk culture of the A. carterae then led to the isolation and structure elucidation of the AM-A derivative named amphidinol C featuring a tetrahydropyran ring between the positions C-7 and C-11. The structure was determined using extensive analyses of NMR data and comparisons with data of already elucidated analogues. The major metabolite was then tested for its antibacterial and antifungal activities and showed moderate fungicidal activity against yeast and filamentous fungi at 8–16 µg mL−1. .
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NUI Galway