Work is supported by a grant from the NIH (AI52230).
Fatty acids -- Biosynthesis, Mass spectrometry, Crystals -- Structure, Antibacterial agents
The fatty acid biosynthesis pathway is an attractive but still largely unexploited target for development of new anti-bacterial agents. The extended use of the anti-tuberculosis drug isoniazid and the antiseptic triclosan, which are inhibitors of fatty acid biosynthesis, validates this pathway as a target for anti-bacterial development. Differences in subcellular organization of the bacterial and eukaryotic multi-enzyme fatty acid synthase systems offer the prospect of inhibitors with host vs. 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 catalogue 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 and Reynolds, Kevin A., "Antibacterial Targets in Fatty Acid Biosynthesis" (2007). Chemistry Faculty Publications and Presentations. 173.