Isolation, enzyme-bound structure, and activity of platensimycin A1 from Streptomyces platensis

✍ Scribed by Sheo B. Singh; Hiranthi Jayasuriya; Kithsiri B. Herath; Chaowei Zhang; John G. Ondeyka; Deborah L. Zink; Sookhee Ha; Gopalakrishnan Parthasarathy; Joseph W. Becker; Jun Wang; Stephen M. Soisson

• Publisher: Elsevier Science
• Year: 2009
• Tongue: French
• Weight: 246 KB
• Volume: 50
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/j.tetlet.2009.06.118

✦ Synopsis

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 A 1 , 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 A 1 suggests that substitution at C-14 is detrimental for the activity.