Vinaxanthone, a new FabI inhibitor from Penicillium sp.

Cited 31 time in scopus
Metadata Downloads
Vinaxanthone, a new FabI inhibitor from Penicillium sp.
C J Zheng; Mi Jin Sohn; Won Gon Kim
Bibliographic Citation
Journal of Antimicrobial Chemotherapy, vol. 63, no. 5, pp. 949-953
Publication Year
Objectives: Bacterial enoyl-ACP reductase (FabI) has been validated as a novel antibacterial target for tackling infections caused by multidrug-resistant pathogens. A few FabI inhibitors, however, are known. This study isolated a new FabI inhibitor from Penicillium sp. Methods: A screening programme led to the selection of a Penicillium sp. producing a strong FabI-inhibitory metabolite. The chemical structure of the isolated FabI inhibitor was elucidated by mass spectrometry and nuclear magnetic resonance spectral data. The antibacterial target of the inhibitor was validated by overexpression assays. Results: The isolated FabI inhibitor was elucidated to be vinaxanthone. It selectively inhibited Staphylococcus aureus FabI with an IC50 of 0.9 μM; it did not affect FabK, an enoyl-ACP reductase of Streptococcus pneumoniae. Consistent with its inhibition of FabI, the inhibitor prevented intracellular fatty acid synthesis while it did not affect protein biosynthesis. It also prevented the growth of S. aureus as well as methicillin-resistant S. aureus (MRSA) and quinolone-resistant S. aureus. Importantly, fabI -overexpressing S. aureus showed reduced susceptibility to the inhibitor compared with the wild-type strain, demonstrating that its antibacterial action is mediated by inhibition of FabI. Conclusions: Vinaxanthone is a new FabI-directed antibacterial of natural origin that could have potential for further development as a new anti-MRSA agent.
antibacterialEnoyl-ACP reductasefatty acid synthesisstaphylococcus aureustarget validation
Oxford Univ Press
Appears in Collections:
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.

Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.