Antibacterial targets in fatty acid biosynthesis.
The fatty acid biosynthesis pathway is an attractive but still largely unexploited target for the development of new antibacterial agents. The extended use of the antituberculosis drug isoniazid and the antiseptic triclosan, which are inhibitors of fatty acid biosynthesis, validates this pathway as a target for antibacterial development. Differences in subcellular organization of the bacterial and eukaryotic multienzyme fatty acid synthase systems offer the prospect of inhibitors with host versus target specificity. Platensimycin, platencin, and phomallenic acids, newly discovered natural product inhibitors of the condensation steps in fatty acid biosynthesis, represent new classes of compounds with antibiotic potential. An almost complete catalog of crystal structures for the enzymes of the type II fatty acid biosynthesis pathway can now be exploited in the rational design of new inhibitors, as well as the recently published crystal structures of type I FAS complexes.
Wright
H Tonie
HT
Department of Biochemistry and Institute of Structural Biology and Drug Discovery, Virginia Commonwealth University, 800 E. Leigh St. Suite 212, Richmond, VA 23219-1540, USA. reynoldsk@pdx.edu
Reynolds
Kevin A
KA
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D015195:Drug Design; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000737:chemistry; D005227:Fatty Acids / Q000096:biosynthesis*; D050356:Lipid Metabolism / Q000187:drug effects*; D054852:Small Molecule Libraries
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005227:Fatty Acids; D054852:Small Molecule Libraries; D064429:Fatty Acid Synthases
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