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Regio‐selectively reduced streptogramin A analogue, 5,6‐dihydrovirginiamycin M 1 exhibits improved potency against MRSA
Author(s) -
Hoang N.H.,
Huong N.L.,
Shrestha A.,
Sohng J.K.,
Yoon Y.J.,
Park J.W.
Publication year - 2013
Publication title -
letters in applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.698
H-Index - 110
eISSN - 1472-765X
pISSN - 0266-8254
DOI - 10.1111/lam.12125
Subject(s) - virginiamycin , antibiotics , chemistry , stereochemistry , antimicrobial , potency , streptomyces , methicillin resistant staphylococcus aureus , antibacterial activity , staphylococcus aureus , combinatorial chemistry , bacteria , microbiology and biotechnology , biochemistry , biology , in vitro , genetics
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 S treptomyces venezuelae . Its chemical structure was spectroscopically elucidated, and this streptogramin A analogue showed twofold higher antibacterial activities against methicillin‐resistant S taphylococcus 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.