| ORIGINAL ARTICLES |
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Micro-scale screening of genetically modified Fusarium fujikuroi strain extends the apicidin family |
| Alica Fischle1,2, Mika Lutsch1, Florian Hübner1, Linda Sch?ker-Hübner3, Lina Schürmann1, Finn K. Hansen3, Svetlana A. Kalinina1,2 |
1. Institute of Food Chemistry, University of Münster, Corrensstra?e 45, 48149 Münster, Germany;
2. Graduate School of Natural Products, Corrensstra?e 43, 48149 Münster, Germany;
3. Pharmaceutical Institute, Pharmaceutical and Cell Biological Chemistry, University of Bonn, An Der Immenburg 4, 53121 Bonn, Germany |
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Abstract Apicidins are a class of naturally occurring cyclic tetrapeptides produced by few strains within the Fusarium genus. These secondary metabolites have gained significant attention due to their antiprotozoal activity through HDAC inhibition, thereby highlighting their potential for the treatment of malaria. Predominantly, apicidins have been isolated from Fusarium semitectum, offering a deep insight into the biosynthetic pathway responsible for their formation. A similar biosynthetic gene cluster has also been identified in the rice pathogenic fungus F. fujikuroi, leading the discovery of three additional apicidins through genetic manipulation. Routine mass spectrometric screening of these compound-producing strains revealed another metabolite structurally related to previously studied apicidins. By optimizing culture conditions and developing an effective isolation method, we obtained a highly pure substance, whose chemical structure was fully elucidated using NMR and HRMS fragmentation. Further studies were conducted to determine cytotoxicity, antimalarial activity, and HDAC inhibitory activity of this new secondary metabolite alongside the previously known apicidins. This work not only expands the apicidin class with a new member but also provides extensive insights and comparative analysis of apicidin-like substances produced by F. fujikuroi.
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| Keywords
Cyclic tetrapeptides
Apicidins
Cytotoxicity
HDAC inhibition
Tropical diseases
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Corresponding Authors:
Svetlana A. Kalinina,E-mail:s_kali03@uni-muenster.de
E-mail: s_kali03@uni-muenster.de
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Issue Date: 13 December 2024
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