Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Panosialins, Inhibitors of Enoyl-ACP Reductase from Streptomyces sp. AN1761

  • Kwon, Yun Ju (Environmental Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Sohn, Mi-Jin (Environmental Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Oh, Taegwon (Department of Microbiology and the Brain Korea 21 Project for the Medical Sciences, Yonsei University College of Medicine) ;
  • Cho, Sang-Nae (Department of Microbiology and the Brain Korea 21 Project for the Medical Sciences, Yonsei University College of Medicine) ;
  • Kim, Chang-Jin (Environmental Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Won-Gon (Environmental Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2012.09.13
  • Accepted : 2012.10.17
  • Published : 2013.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

In the continued search for inhibitors of enoyl-acyl carrier protein (ACP) reductase, we found that four acylbenzenediol sulfate metabolites from Streptomyces sp. AN1761 potently inhibited bacterial enoyl-ACP reductases of Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. Their structures were identified as panosialins A, B, wA, and wB by MS and NMR data. They showed stronger inhibition against S. aureus FabI and S. pneumoniae FabK with $IC_{50}$ of 3-5 ${\mu}M$ than M. tuberculosis InhA with $IC_{50}$ of 9-12 ${\mu}M$. They also exhibited a stronger antibacterial spectrum on S. aureus and S. pneumoniae than M. tuberculosis. In addition, the higher inhibitory activity of panosialin wB than panosialin B on fatty acid biosynthesis was consistent with that on bacterial growth, suggesting that they could exert their antibacterial activity by inhibiting fatty acid synthesis.

Keywords

References

  1. Aoyagi, T., M. Yagisawa, M. Kumagai, M. Hamada, Y. Okami, T. Takeuchi, and H. Umezawa. 1971. An enzyme inhibitor, panosialin, produced by Streptomyces. I. Biological activity, isolation and characterization of panosialin. J. Antibiot. 24: 860-869. https://doi.org/10.7164/antibiotics.24.860
  2. Campbell, J. W. and J. E. Cronan. 2001. Bacterial fatty acid biosynthesis: Targets for antibacterial drug discovery. Annu. Rev. Microbiol. 55: 305-332. https://doi.org/10.1146/annurev.micro.55.1.305
  3. Collins, L. A., M. N. Torrero, and S. G. Franzblau. 1998. Green fluorescent protein reporter microplate assay for highthroughput screening of compounds against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 42: 344-347.
  4. Heath, R. J. and C. O. Rock. 2004. Fatty acid biosynthesis as a target for novel antibacterials. Curr. Opin. Investig. Drugs 5: 146-153
  5. Kumagai, M., Y. Suhara, T. Aoyagi, and H. Umezawa. 1971. An enzyme inhibitor, panosialin, produced by Streptomyces. II. Chemistry of panosialin, 5-alkylbenzene-1,3-disulfates. J. Antibiot. 24: 870-875. https://doi.org/10.7164/antibiotics.24.870
  6. Kwon, Y. J., Y. Fang, G. H. Xu, and W. G. Kim. 2009. Aquastatin A, a new inhibitor of enoyl-acyl carrier protein reductase from Sporothrix sp. FN611. Biol. Pharm. Bull. 32: 2061-2064. https://doi.org/10.1248/bpb.32.2061
  7. McMurry, L. M., M. Oethinger, and S. B. Levy. 1998. Triclosan targets lipid synthesis. Nature 394: 531-532. https://doi.org/10.1038/28970
  8. Moir, D. T. 2005. Identification of inhibitors of bacterial enoylacyl carrier protein reductase. Curr. Drug Targets Infect. Disord. 5: 297-305. https://doi.org/10.2174/1568005054880154
  9. Rozwarski, D. A., G. A. Grant, D. H. R. Barton, W. R. Jacobs Jr., and J. C. Sacchettini. 1998. Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Science 279: 98-102. https://doi.org/10.1126/science.279.5347.98
  10. Yamada, H., K. Shiomi, Q. Xu, T. Nagai, M. Shibata, I. Oya, et al. 1995. New glycosidases inhibitors, panosialins D and wD produced by Streptomyces sp. OH-5186. J. Antibiot. 48: 205-210 https://doi.org/10.7164/antibiotics.48.205
  11. Zhang, Y. M., S. W. White, and C. O. Rock. 2006. Inhibiting bacterial fatty acid synthesis. J. Biol. Chem. 281: 17541-17544. https://doi.org/10.1074/jbc.R600004200
  12. Zheng, C. J., M. J. Sohn, S.-W. Chi, and W. G. Kim. 2010. Methyl-branched fatty acids, inhibitors of enoyl-ACP reductase with antibacterial activity from Streptomyces sp. A251. J. Microbiol. Biotechnol. 20: 875-880. https://doi.org/10.4014/jmb.1001.01004
  13. Zheng, C. J., M. J. Sohn, and W. G. Kim. 2009. Vinaxanthone, a new FabI inhibitor from Penicillium sp. J. Antimicrob. Chemother. 63: 949-953. https://doi.org/10.1093/jac/dkp058

Cited by

  1. Recent advances in inhibitors of bacterial fatty acid synthesis type???II (FASII) system enzymes as potential antibacterial agents. vol.8, pp.10, 2013, https://doi.org/10.1002/cmdc.201300209