The polyether antibiotics are a large group of structurally related polyketide natural products, mainly of bacterial origin, which efficiently complex Group I or II metal cations (1). One well known example is the commercially important coccidiostat and growth promoter, monensin A (1) (see Fig. 1). Embedded within its carbon backbone is a complex array of functional groups that allow tight and specific binding of Na+ions. How this binding is achieved can be largely appreciated from a consideration of the monensin A-Na+X-ray crystal structure (2) (Fig. 2). The relative configuration of the molecule and the disposition of six oxygen atoms within or appended to the five heterocyclic rings allow the backbone to fold and create a cavity whose size exactly matches the ionic radius and ligand requirements of Na+. In addition, a pair of hydrogen bonds is formed between the carboxylate oxygens at C1 and the two hydroxyl groups at C25 and C26, which tether the ends of the molecule together generating a shell which encompasses the metal ion. The exterior of the complex possesses a uniform hydrophobic surface which is ideal for diffusion through a lipid environment. The transport of metal ions across cell membranes mediated by the polyether antibiotics frequently leads to uncoupling of oxidative phosphorylation and ultimately to cell death (1).


Fatty Acid Biosynthesis Macrolide Antibiotic Acyl Carrier Protein Biochemical Aspect Enoyl Reductase 
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Copyright information

© Springer-Verlag/Wien 1991

Authors and Affiliations

  • J. A. Robinson
    • 1
  1. 1.Organisch-Chemisches InstitutUniversität ZürichZürichSwitzerland

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