Author/Authors :
Singh، نويسنده , , Sheo B. and Jayasuriya، نويسنده , , Hiranthi and Herath، نويسنده , , Kithsiri B. and Zhang، نويسنده , , Chaowei and Ondeyka، نويسنده , , John G. and Zink، نويسنده , , Deborah L. and Ha، نويسنده , , Sookhee and Parthasarathy، نويسنده , , Gopalakrishnan and Becker، نويسنده , , Joseph W. and Wang، نويسنده , , Jun and Soisson، نويسنده , , Stephen M.، نويسنده ,
Abstract :
Inhibition of fatty acid synthesis is emerging as a valuable target for antibacterial agents. Platensimycin and platencin are novel natural products that were reported recently to inhibit the FabF and FabF/FabH condensing enzymes, respectively, present in the fatty acid biosynthetic pathway. Selective inhibition of these enzymes by platensimycin and platencin accounts for their potent antibiotic activity. We have continued our quest to find additional members of this class of compounds leading to discovery of platensimycin A1, a hydroxylated congener. We report herein the isolation, structure, antibacterial and enzymatic activities, and co-crystal structure bound to Escherichia coli FabF. The lower activity of platensimycin A1 suggests that substitution at C-14 is detrimental for the activity.
