Regio-selectively reduced streptogramin A analogue, 5,6-dihydrovirginiamycin M1 exhibits improved potency against MRSA

N. H. Hoang, N. L. Huong, A. Shrestha, J. K. Sohng, Y. J. Yoon, J. W. Park

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A newly reduced macrocyclic lactone antibiotic streptogramin A, 5,6-dihydrovirginiamycin M1 was created by feeding virginiamycin M1 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 M1. 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 M1. 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. Significance and Impact of the Study: This study demonstrates the expanded applicability of the unique bio-hydrogenation activity of Streptomyces venezuelae towards macrocyclic lactone streptogramin A antibiotic and evaluates the enhanced anti-MRSA activity of the bioconverted analogue. The unique bio-catalytic feature of S. venezuelae could contribute to the biosynthesis and reconstruction of diverse therapeutic resources, particularly as a promising scaffold tailoring tool for creating antimicrobial agents with possibly improved therapeutic effects. Significance and Impact of the Study: This study demonstrates the expanded applicability of the unique bio-hydrogenation activity of Streptomyces venezuelae towards macrocyclic lactone streptogramin A antibiotic and evaluates the enhanced anti-MRSA activity of the bioconverted analogue. The unique bio-catalytic feature of S. venezuelae could contribute to the biosynthesis and reconstruction of diverse therapeutic resources, particularly as a promising scaffold tailoring tool for creating antimicrobial agents with possibly improved therapeutic effects.

Original languageEnglish
Pages (from-to)393-398
Number of pages6
JournalLetters in Applied Microbiology
Volume57
Issue number5
DOIs
Publication statusPublished - 2013 Nov
Externally publishedYes

Keywords

  • Enhanced anti-MRSA activity
  • Microbial biocatalyst
  • Reduced macrocyclic lactone
  • Streptogramin A antibiotic
  • Streptomyces venezuelae

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology

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