Inhibitors of fatty acid synthesis as antimicrobial chemotherapeutics.
Fatty acid biosynthesis is an emerging target for the development of novel antibacterial chemotherapeutics. The dissociated bacterial system is substantially different from the large, multifunctional protein of mammals, and many possibilities exist for type-selective drugs. Several compounds, both synthetic and natural, target bacterial fatty acid synthesis. Three compounds target the FabI enoyl-ACP reductase step; isoniazid, a clinically used antituberculosis drug, triclosan, a widely used consumer antimicrobial, and diazaborines. In addition, cerulenin and thiolactomycin, two fungal products, inhibit the FabH, FabB and FabF condensation enzymes. Finally, the synthetic reaction intermediates BP1 and decynoyl- N-acetyl cysteamine inhibit the acetyl-CoA carboxylase and dehydratase isomerase steps, respectively. The mechanisms of action of these compounds, as well as the potential development of new drugs targeted against this pathway, are discussed.
Heath
R J
RJ
Protein Science Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis TN 38105, USA. richard.heath@stjude.org
White
S W
SW
Rock
C O
CO
D000890:Anti-Infective Agents / Q000494:pharmacology*; D004798:Enzymes / Q000378:metabolism; D005227:Fatty Acids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000890:Anti-Infective Agents; D004798:Enzymes; D005227:Fatty Acids