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| Lipid biosynthesis as a target for antibacterial agents |
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| Author(s): Heath RJ, White SW, Rock CO |
| Source: PROGRESS IN LIPID RESEARCH Volume: 40 Issue: 6 Pages: 467-497 Published: NOV 2001 |
| Times Cited: 145 References: 206 |
| Abstract: Fatty acid biosynthesis, the first stage in membrane lipid biogenesis, is catalyzed in most bacteria by a series of small, soluble proteins that are each encoded by a discrete gene (Fig. 1; Table 1). This arrangement is termed the type II fatty acid synthase (FAS) system and contrasts sharply with the type I FAS of eukaryotes which is a dimer of a single large, multifunctional polypeptide. Thus, the bacterial pathway offers several unique sites for selective inhibition by chemotherapeutic agents. The site of action of isoniazid, used in the treatment of tuberculosis for 50 years, and the consumer antimicrobial agent triclosan were revealed recently to be the enoyl-ACP reductase of the type II FAS. The fungal metabolites, cerulenin and thiolactomycin, target the condensing enzymes of the bacterial pathway while the dehydratase/isomerase is inhibited by a synthetic acetylenic substrate analogue. Transfer of fatty acids to the membrane has also been inhibited via interference with the first acyltransferase step, while a new class of drugs targets lipid A synthesis. This review will summarize the data generated on these inhibitors to date, and examine where additional efforts will be required to develop new chemo therapeutics to help combat microbial infections. (C) 2001 Elsevier Science Ltd. All rights reserved. |
| Document Type: Review |
| Language: English |
| Reprint Address: Heath, RJ (reprint author), St Jude Childrens Hosp, Dept Infect Dis, Prot Sci Div, 332 N Lauderdale St, Memphis, TN 38105 USA |
Addresses:
1. St Jude Childrens Hosp, Dept Infect Dis, Prot Sci Div, Memphis, TN 38105 USA
2. St Jude Childrens Hosp, Dept Biol Struct, Memphis, TN 38105 USA
3. Univ Tennessee, Dept Mol Biosci, Memphis, TN 38163 USA |
| Publisher: PERGAMON-ELSEVIER SCIENCE LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology; Nutrition & Dietetics |
| IDS Number: 485WL |
| ISSN: 0163-7827 |
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