Journal
MICROORGANISMS
Volume 10, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/microorganisms10030626
Keywords
laccase; biotransformation; aminoglycoside antibiotics; cytotoxicity; antimicrobial activity; multidrug resistance (MDR); beta-lactam antibiotics; methicillin-resistant Staphylococcus aureus (MRSA); antimicrobial resistance (AMR)
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Research on the synthesis of new antibiotics using laccase has successfully produced new aminoglycoside antibiotics with promising antibacterial activity and low cytotoxicity. These synthesized products showed comparable or even better antibacterial activity than parent antibiotics and protected mice from Staphylococcus aureus infection. This highlights the potential of laccases in obtaining new antibiotic candidates.
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 beta-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-N-(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 Staphylococcus aureus, 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.
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