Abstract
Platensimycin and platencin are inhibitors of FabF and FabF/H bacterial fatty acid synthesis enzymes, respectively. Discovery of natural congeners provides one of the ways to understand the relationship of chemical structure and biological function. Efforts to discover the natural analogs of platensimycin by chemical screening led to the isolation of platensimycin B4, a glucoside congener of platensimycin. This analog showed significantly attenuated activity and critically defined the limited binding space around the aromatic ring and established the importance of the free phenolic and carboxyl group for the activity.
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References
Wang, J. et al. Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature. 441, 358–361 (2006).
Singh, S. B. et al. Isolation, structure, and absolute stereochemistry of platensimycin, a broad spectrum antibiotic discovered using an antisense differential sensitivity strategy. J. Am. Soc. 128, 11916–11920. and 15547 (2006).
Jayasuriya, H. et al. Isolation and structure of platencin: a novel FabH and FabF dual inhibitor with potent broad spectrum antibiotic activity produced by Streptomyces platensis MA7339. Angew. Chem. Int. Ed. 46, 4684–4688 (2007).
Wang, J. et al. Platencin is a dual FabF and FabH inhibitor with potent in vivo antibiotic properties. Proc. Natl Acad. Sci. (USA) 104, 7612–7616 (2007).
Young, K. et al. Discovery of FabH/FabF inhibitors from natural products. Antimicrob. Agents. Chemother. 50, 519–526 (2006).
Singh, S. B., Phillips, J. W. & Wang, J. Highly sensitive target based whole cell antibacterial discovery strategy by antisense RNA silencing. Curr. Opin. Drug. Disc. Dev. 10, 160–166 (2007).
Singh, S. B., Herath, K. B., Wang, J., Tsou, N. N. & Ball, R. G. Chemistry of platensimycin. Tetrahedron. Lett. 48, 5429–5433 (2007).
Shen, H. C. et al. Synthesis and biological evaluation of platensimycin analogs. Bioorg. Med. Chem. Lett. 19, 1623–1627 (2009).
Herath, K. B. et al. Structure and semisynthesis of platensimide A, produced by Streptomyces platensis. Org. Lett. 10, 1699–1702 (2008).
Jayasuriya, H. et al. Structure of homoplatensimide A: a potential key biosynthetic intermediate of platensimycin isolated from Streptomyces platensis. Tetrahedron. Lett. 49, 3648–3651 (2008).
Zhang, C. et al. Isolation, structure and fatty acid synthesis inhibitory activities of platensimycin B1-B3 from Streptomyces platensis. Chem. Commun. (Camb) 5034–5036 (2008).
Singh, S. B. et al. Isolation, enzyme-bound structure and antibacterial activity of platensimycin a1 from Streptomyces platensis. Tetrahedron. Lett. 50, 5182–5185 (2009).
Singh, S. B. et al. Isolation, enzyme-bound structure and antibacterial activity of platencin A1 from Streptomyces platensis. Bioorg. Med. Chem. Lett. 19, 4756–4759 (2009).
Kodali, S. et al. Determination of selectivity and efficacy of fatty acid synthesis inhibitors. J. Biol. Chem. 280, 1669–1677 (2005).
Young, K. & Silver, L. L. Leakage of periplasmic enzymes from enva1 strains of escherichia coli. J. Bacteriol. 173, 3609–3614 (1991).
Markham, P. N. & Neyfakh, A. A. Efflux-mediated drug resistance in Gram-positive bacteria. Curr. Opin. Microbiol. 4, 509–514 (2001).
Acknowledgements
We thank S Kodali, A Galgoci, K Young, R Painter, M Motyl and K Dorso for some of the initial biological results.
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Zhang, C., Ondeyka, J., Guan, Z. et al. Isolation, structure and biological activities of platensimycin B4 from Streptomyces platensis. J Antibiot 62, 699–702 (2009). https://doi.org/10.1038/ja.2009.106
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DOI: https://doi.org/10.1038/ja.2009.106
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