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

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...

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Vydáno v:Letters in applied microbiology Ročník 57; číslo 5; s. 393 - 398
Hlavní autoři: Hoang, N.H., Huong, N.L., Shrestha, A., Sohng, J.K., Yoon, Y.J., Park, J.W.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Oxford Blackwell 01.11.2013
Oxford University Press
Témata:
Acetyltransferase
Anti-Bacterial Agents - pharmacology
Antimicrobial agents
Biological and medical sciences
Biosynthesis
Biotransformation
enhanced anti‐MRSA activity
Fundamental and applied biological sciences. Psychology
Methicillin-Resistant Staphylococcus aureus - drug effects
microbial biocatalyst
Microbiology
reduced macrocyclic lactone
Staphylococcus aureus
Streptogramin A - analogs & derivatives
Streptogramin A - biosynthesis
Streptogramin A - chemistry
Streptogramin A - pharmacology
streptogramin A antibiotic
Streptomyces venezuelae
Virginiamycin - metabolism
Streptomycetaceae
reduced macrocyclic lactone
Applied microbiology
Streptomyces venezuelae
Lactone
Biocatalyst
Macrocycle
Actinomycetales
Antibiotic
streptogramin A antibiotic
microbial biocatalyst
Analog
Bacteria
Actinomycetes
Microorganism
enhanced anti-MRSA activity
ISSN:0266-8254, 1472-765X, 1472-765X
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Shrnutí: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.
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ISSN:0266-8254
1472-765X
1472-765X
DOI:10.1111/lam.12125