Laccase-Catalyzed Derivatization of Aminoglycoside Antibiotics and Glucosamine
The increasing demand for new and effective antibiotics requires intelligent strategies to obtain a wide range of potential candidates. Laccase-catalyzed reactions have been successfully applied to synthesize new β-lactam antibiotics and other antibiotics. In this work, laccases from three different...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/3/626 |
| _version_ | 1797444681335832576 |
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| author | Annett Mikolasch Ulrike Lindequist Sabine Witt Veronika Hahn |
| author_facet | Annett Mikolasch Ulrike Lindequist Sabine Witt Veronika Hahn |
| author_sort | Annett Mikolasch |
| collection | DOAJ |
| description | The increasing demand for new and effective antibiotics requires intelligent strategies to obtain a wide range of potential candidates. Laccase-catalyzed reactions have been successfully applied to synthesize new β-lactam antibiotics and other antibiotics. In this work, laccases from three different origins were used to produce new aminoglycoside antibiotics. Kanamycin, tobramycin and gentamicin were coupled with the laccase substrate 2,5-dihydroxy-<i>N</i>-(2-hydroxyethyl)-benzamide. The products were isolated, structurally characterized and tested in vitro for antibacterial activity against various strains of Staphylococci, including multidrug-resistant strains. The cytotoxicity of these products was tested using FL cells. The coupling products showed comparable and, in some cases, better antibacterial activity than the parent antibiotics in the agar diffusion assay, and they were not cytotoxic. The products protected mice against infection with <i>Staphylococcus aureus</i>, which was lethal to the control animals. The results underline the great potential of laccases in obtaining new biologically active compounds, in this case new antibiotic candidates from the class of aminoglycosides. |
| first_indexed | 2024-03-09T13:15:05Z |
| format | Article |
| id | doaj.art-fdf30221022649f38a7709a030518c23 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T13:15:05Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-fdf30221022649f38a7709a030518c232023-11-30T21:37:09ZengMDPI AGMicroorganisms2076-26072022-03-0110362610.3390/microorganisms10030626Laccase-Catalyzed Derivatization of Aminoglycoside Antibiotics and GlucosamineAnnett Mikolasch0Ulrike Lindequist1Sabine Witt2Veronika Hahn3Institute for Microbiology, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, GermanyInstitute of Pharmacy, University of Greifswald, Friedrich-Ludwig-Jahn-Str. 17, 17487 Greifswald, GermanyBiometec, Walther-Rathenau-Str. 49a, 17489 Greifswald, GermanyInstitute for Microbiology, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, GermanyThe increasing demand for new and effective antibiotics requires intelligent strategies to obtain a wide range of potential candidates. Laccase-catalyzed reactions have been successfully applied to synthesize new β-lactam antibiotics and other antibiotics. In this work, laccases from three different origins were used to produce new aminoglycoside antibiotics. Kanamycin, tobramycin and gentamicin were coupled with the laccase substrate 2,5-dihydroxy-<i>N</i>-(2-hydroxyethyl)-benzamide. The products were isolated, structurally characterized and tested in vitro for antibacterial activity against various strains of Staphylococci, including multidrug-resistant strains. The cytotoxicity of these products was tested using FL cells. The coupling products showed comparable and, in some cases, better antibacterial activity than the parent antibiotics in the agar diffusion assay, and they were not cytotoxic. The products protected mice against infection with <i>Staphylococcus aureus</i>, which was lethal to the control animals. The results underline the great potential of laccases in obtaining new biologically active compounds, in this case new antibiotic candidates from the class of aminoglycosides.https://www.mdpi.com/2076-2607/10/3/626laccasebiotransformationaminoglycoside antibioticscytotoxicityantimicrobial activitymultidrug resistance (MDR) |
| spellingShingle | Annett Mikolasch Ulrike Lindequist Sabine Witt Veronika Hahn Laccase-Catalyzed Derivatization of Aminoglycoside Antibiotics and Glucosamine Microorganisms laccase biotransformation aminoglycoside antibiotics cytotoxicity antimicrobial activity multidrug resistance (MDR) |
| title | Laccase-Catalyzed Derivatization of Aminoglycoside Antibiotics and Glucosamine |
| title_full | Laccase-Catalyzed Derivatization of Aminoglycoside Antibiotics and Glucosamine |
| title_fullStr | Laccase-Catalyzed Derivatization of Aminoglycoside Antibiotics and Glucosamine |
| title_full_unstemmed | Laccase-Catalyzed Derivatization of Aminoglycoside Antibiotics and Glucosamine |
| title_short | Laccase-Catalyzed Derivatization of Aminoglycoside Antibiotics and Glucosamine |
| title_sort | laccase catalyzed derivatization of aminoglycoside antibiotics and glucosamine |
| topic | laccase biotransformation aminoglycoside antibiotics cytotoxicity antimicrobial activity multidrug resistance (MDR) |
| url | https://www.mdpi.com/2076-2607/10/3/626 |
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