Platensimycin

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IUPACName = 3- [ [3- [(1R,3R,4R,5aR,9R,9aS)
-1,4,5,8,9,9a-hexahydro-3,9-dimethyl
-8-oxo-3H-1,4:3,5a-dimethano
-2-benzoxepin-9-yl] -1-oxopropyl] amino]
-2,4-dihydroxy-benzoic acid
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C=24|H=27|N=1|O=7
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Platensimycin is a member of a previously unknown class of antibiotics, which acts by blocking enzymes involved in the of the condensation steps in fatty acid biosynthesis, [Dieter Häbich, Franz von Nussbaum, "ChemMedChem" 2006, "1", 951–954. Platensimycin, a new antibiotic and "superbug challenger" from nature. PMID 16952137] which Gram-positive bacteria need to biosynthesise cell membranes (β-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B)). Other enzymes in this pathway have similarly been proven antibiotic targets for example FabI, the enoyl-ACP (acyl carrier protein) reductase, that is inhibited by isoniazid and related compounds and the antiseptic agent triclosan. [H T. Wright, and K.A Reynolds (2007) Antibacterial targets in fatty acid biosynthesis. Current Opinion in Microbiology doi:10.1016/j.mib.2007.07.001] It is an experimental new drug in preclinical trials in an effort to combat MRSA in a mouse model.Jun Wang "et al", "Platensimycin is a selective FabF inhibitor with potent antibiotic properties", Nature 441, 358-361 (18 May 2006) PMID 16710421] Platensimycin is a very effective antibiotic in vivo when continuously administered to cells, however this efficiency is reduced when administered by more conventional means.K B. Herath, A B. Attygalle, and S B. Singh (2007) Biosynthetic Studies of Platensimycin. JACS Communications 11/23/2007 PMID 18034483] The biosynthesis of plantensimycin has been studied using isotope incorporation experiments to show that the benzoic ring is produced from pyruvate and acetate via the TCA cycle, while the C-17 tetracyclic enone acid core is produced from the non-mevalonate terpenoid pathway.

This natural product was first isolated from a strain of "Streptomyces platensis" by the Merck group. A first total synthesis of racemic platensimycin has been published.K. C. Nicolaou, A. Li, D. J. Edmonds, "Angew. Chem." 2006, "118", 7244 – 7248; "Angew. Chem. Int. Ed." 2006, "45", 7086 – 7090. PMID 17013803] Its structure consists of a 3-amino-2,4-dihydroxybenzoic acid polar part linked through an amine bond to a lipophilic pentacyclicketolide.

References

External links

* [http://news.bbc.co.uk/1/hi/health/4992696.stm BBC News]
* [http://www.smm.org/buzz/buzz_tags/platensimycin Science news stories on Platensimycin]
* [http://www.nature.com/nature/journal/v441/n7091/abs/nature04784.html Abstract in Nature: Platensimycin is a selective FabF inhibitor with potent antibiotic properties]