Regio-selectively reduced streptogramin A analogue, 5,6-dihydrovirginiamycin M-1 exhibits improved potency against MRSA
- 주제(키워드) enhanced anti-MRSA activity , microbial biocatalyst , reduced macrocyclic lactone , streptogramin A antibiotic , Streptomyces venezuelae
- 등재 SCIE, SCOPUS
- 발행기관 WILEY-BLACKWELL
- 발행년도 2013
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000091346
- 본문언어 영어
- Published As http://dx.doi.org/10.1111/lam.12125
초록/요약
A newly reduced macrocyclic lactone antibiotic streptogramin A, 5,6-dihydrovirginiamycin M1 was created by feeding virginiamycin M-1 into a culture of recombinant Streptomyces venezuelae. Its chemical structure was spectroscopically elucidated, and this streptogramin A analogue showed twofold higher antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) compared with its parent molecule virginiamycin M-1. Docking studies using the model of streptogramin A acetyltransferase (VatA) suggested that the newly generated analogue binds tighter with overall lower free energy compared with the parent molecule virginiamycin M-1. This hypothesis was validated experimentally through the improvement of efficacy of the new analogue against MRSA strains. The biotransformation approach presented herein could have a broad application in the production of reduced macrocyclic molecules.
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