Mikolasch Annett, Lindequist Ulrike, Witt Sabine, Hahn Veronika
Institute for Microbiology, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, Germany.
Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, Germany.
Microorganisms. 2022 Mar 15;10(3):626. doi: 10.3390/microorganisms10030626.
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--(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 , 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.
对新型有效抗生素的需求不断增加，这需要采用智能策略来获取广泛的潜在候选药物。漆酶催化反应已成功应用于合成新型β-内酰胺抗生素和其他抗生素。在这项工作中，使用了来自三种不同来源的漆酶来生产新型氨基糖苷类抗生素。卡那霉素、妥布霉素和庆大霉素与漆酶底物2,5-二羟基-（2-羟乙基）-苯甲酰胺偶联。对产物进行分离、结构表征，并在体外测试其对包括多重耐药菌株在内的各种葡萄球菌菌株的抗菌活性。使用FL细胞测试了这些产物的细胞毒性。在琼脂扩散试验中，偶联产物显示出与母体抗生素相当的抗菌活性，在某些情况下甚至更好，并且它们没有细胞毒性。这些产物保护小鼠免受对对照动物致命的感染。结果强调了漆酶在获取新的生物活性化合物方面的巨大潜力，在这种情况下是从氨基糖苷类中获得新的抗生素候选物。
