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| Format: | Recurso digital |
| Language: | English |
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2022
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| Online Access: | https://doi.org/10.5281/zenodo.16950376 |
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| author | Interdisciplinary Centre of Marine and Environmental Research |
| author_facet | Interdisciplinary Centre of Marine and Environmental Research |
| contents | <p>Over the past decades, cyanobacteria were recognized as fruitful producers of secondary metabolites that inspired approved anticancer drugs. </p> <p>In order to better explore the chemical diversity of the cyanobacterial strains of Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC - CIIMAR) collection, a natural products library of cyanobacterial fractions (LEGE-NPL) was established [1]. From this newly created library, the cyanobacterium <em>Lusitaniella coriacea</em> LEGE 07167 was selected after analysis of its LC-MS/MS data and dereplication, showing the presence of unknown metabolites. </p> <p>Following the scale up biomass production of <em>Lusitaniella coriacea</em> LEGE 07167, and several isolation steps, four novel compounds (lusichelins A-D) were isolated, guided by LC-MS/MS, intercalated with bioactivity assays 2D and 3D cultures of cancer cells. </p> <p>The structure of lusichelins was elucidated by means of 1D and 2D NMR techniques alongside with MS/MS experiments. The stereochemistry is being investigated via experimental and DFT- calculated ECD measurements.</p> <p>The analysis of the genome with antiSMASH showed one biosynthetic gene cluster (BGC) candidate of hybrid PKS-NRPS. This BGC contains four NRPS modules with specific domains for cysteine heterocyclization and oxidation, consistent with thiazol/thiazoline moieties. The BGC also encodes two PKS modules and a salicylate synthase, which is compatible with the other functionalities present in the structure of lusichelins. Moreover, genes encoding siderophore- related transporters and regulatory genes were also present. We searched for other possible derivatives, thus isolating lusichelin E (chelated and not chelated with iron). Lusichelins ionophore capacity was assessed for several metals, as well as, their production in iron-depleted and iron- rich growth conditions.</p> <p>Cytotoxic activity of lusichelins was tested against cancer cells (2D and 3D), and their potential as reversers of multidrug resistance- mediated by P-glycoprotein was evaluated using L5178Y-mouse lymphoma cells.</p> <p>[1] Ferreira et al Mar. Drugs 2021, 19, 633.</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_16950376 |
| institution | Zenodo |
| language | eng |
| publishDate | 2022 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Discovery and isolation of new cyanobacterial salicyl capped-thiazol(in)e siderophores Interdisciplinary Centre of Marine and Environmental Research <p>Over the past decades, cyanobacteria were recognized as fruitful producers of secondary metabolites that inspired approved anticancer drugs. </p> <p>In order to better explore the chemical diversity of the cyanobacterial strains of Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC - CIIMAR) collection, a natural products library of cyanobacterial fractions (LEGE-NPL) was established [1]. From this newly created library, the cyanobacterium <em>Lusitaniella coriacea</em> LEGE 07167 was selected after analysis of its LC-MS/MS data and dereplication, showing the presence of unknown metabolites. </p> <p>Following the scale up biomass production of <em>Lusitaniella coriacea</em> LEGE 07167, and several isolation steps, four novel compounds (lusichelins A-D) were isolated, guided by LC-MS/MS, intercalated with bioactivity assays 2D and 3D cultures of cancer cells. </p> <p>The structure of lusichelins was elucidated by means of 1D and 2D NMR techniques alongside with MS/MS experiments. The stereochemistry is being investigated via experimental and DFT- calculated ECD measurements.</p> <p>The analysis of the genome with antiSMASH showed one biosynthetic gene cluster (BGC) candidate of hybrid PKS-NRPS. This BGC contains four NRPS modules with specific domains for cysteine heterocyclization and oxidation, consistent with thiazol/thiazoline moieties. The BGC also encodes two PKS modules and a salicylate synthase, which is compatible with the other functionalities present in the structure of lusichelins. Moreover, genes encoding siderophore- related transporters and regulatory genes were also present. We searched for other possible derivatives, thus isolating lusichelin E (chelated and not chelated with iron). Lusichelins ionophore capacity was assessed for several metals, as well as, their production in iron-depleted and iron- rich growth conditions.</p> <p>Cytotoxic activity of lusichelins was tested against cancer cells (2D and 3D), and their potential as reversers of multidrug resistance- mediated by P-glycoprotein was evaluated using L5178Y-mouse lymphoma cells.</p> <p>[1] Ferreira et al Mar. Drugs 2021, 19, 633.</p> |
| title | Discovery and isolation of new cyanobacterial salicyl capped-thiazol(in)e siderophores |
| url | https://doi.org/10.5281/zenodo.16950376 |