Regio-selectively reduced streptogramin A analogue, 5,6-dihydrovirginiamycin M 1 exhibits improved potency against MRSA

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A newly reduced macrocyclic lactone antibiotic streptogramin A, 5,6-dihydrovirginiamycin M 1 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 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 1
Externally publishedYes

Fingerprint

Streptogramin A
Methicillin-Resistant Staphylococcus aureus
Streptomyces
Lactones
Virginiamycin
Hydrogenation
Therapeutic Uses
Anti-Bacterial Agents
Anti-Infective Agents
Acetyltransferases
Biotransformation

Keywords

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

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology

Cite this

Regio-selectively reduced streptogramin A analogue, 5,6-dihydrovirginiamycin M 1 exhibits improved potency against MRSA . / Hoang, N. H.; Huong, N. L.; Shrestha, A.; Sohng, J. K.; Yoon, Y. J.; Park, Je Won.

In: Letters in Applied Microbiology, Vol. 57, No. 5, 01.11.2013, p. 393-398.

Research output: Contribution to journalArticle

Hoang, N. H. ; Huong, N. L. ; Shrestha, A. ; Sohng, J. K. ; Yoon, Y. J. ; Park, Je Won. / Regio-selectively reduced streptogramin A analogue, 5,6-dihydrovirginiamycin M 1 exhibits improved potency against MRSA In: Letters in Applied Microbiology. 2013 ; Vol. 57, No. 5. pp. 393-398.
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