Structure-Antibacterial Activity Relationship of Cyclic Lipodepsipeptide Antibiotic Fusaricidin A

摘要

Fusaricidin A is a cyclic lipodepsipeptide originally isolated from Bacillus polymyxa KT-8 strain, and exhibits promising activity against various kinds of fungi and Gram-positive bacteria, including methicillin-resistant S. aureus [1]. Fusaricidin's relatively simple structure and potent antimicrobial activity make this natural product particularly interesting lead structure for the development of new and more potent antibiotics. In order to investigate structural basis for fusaricidin's antimicrobial activity, and to define its minimal bioactive pharmacophore, we have synthesized fusaricidin A's analogs that differ in the lipid tail part and alanine-scanning analogs. Defining the minimal structural requirements responsible for fusaricidin's antibiotic activity may facilitate chemical synthesis of the antibiotic by reducing structural complexity and promote judicious chemical modifications for modulation of its pharmacological or physiochemical properties.