Abstract
Platensimycin was recently discovered by Merck Research Laboratories and has created considerable interest given its potent antibacterial activity and mode of action. The use of RNA gene-silencing techniques and screening libraries of natural products allowed Merck to find this antibiotic which may have otherwise been missed using conventional methods. Interestingly, platensimycin has shown good activity against a panel of Gram positive organisms which included various resistant strains. Platensimycin works by inhibiting β- ketoacyl synthases I/II (FabF/B) which are key enzymes in the production of fatty acids required for bacterial cell membranes. So far, a number of groups have explored synthetic strategies for platensimycin and this work has subsequently lead to the synthesis of active analogues. Given its mode of action, it is intriguing as to why Merck themselves patented only a single compound and have not apparently sought to generate further libraries. This review will discuss the origins of platensimycin, its mechanism of action, synthetic schemes and where the future may take us following this fascinating discovery.
Keywords: Platensimycin, Streptomyces platensis, β-ketoacyl synthases I/II (FabF/B) inhibition, platencin, drug resistance, natural products, antibiotics, fatty acid synthesis
Current Medicinal Chemistry
Title: Platensimycin: A Promising Antimicrobial Targeting Fatty Acid Synthesis
Volume: 15 Issue: 7
Author(s): D. T. Manallack, I. T. Crosby, Y. Khakham and B. Capuano
Affiliation:
Keywords: Platensimycin, Streptomyces platensis, β-ketoacyl synthases I/II (FabF/B) inhibition, platencin, drug resistance, natural products, antibiotics, fatty acid synthesis
Abstract: Platensimycin was recently discovered by Merck Research Laboratories and has created considerable interest given its potent antibacterial activity and mode of action. The use of RNA gene-silencing techniques and screening libraries of natural products allowed Merck to find this antibiotic which may have otherwise been missed using conventional methods. Interestingly, platensimycin has shown good activity against a panel of Gram positive organisms which included various resistant strains. Platensimycin works by inhibiting β- ketoacyl synthases I/II (FabF/B) which are key enzymes in the production of fatty acids required for bacterial cell membranes. So far, a number of groups have explored synthetic strategies for platensimycin and this work has subsequently lead to the synthesis of active analogues. Given its mode of action, it is intriguing as to why Merck themselves patented only a single compound and have not apparently sought to generate further libraries. This review will discuss the origins of platensimycin, its mechanism of action, synthetic schemes and where the future may take us following this fascinating discovery.
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Cite this article as:
Manallack T. D., Crosby T. I., Khakham Y. and Capuano B., Platensimycin: A Promising Antimicrobial Targeting Fatty Acid Synthesis, Current Medicinal Chemistry 2008; 15 (7) . https://dx.doi.org/10.2174/092986708783885255
DOI https://dx.doi.org/10.2174/092986708783885255 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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