Metal Binding and Structure–Activity Relationship of the Metalloantibiotic Peptide Bacitracin
a focused review in the Journal of Inorganic Biochemistry, 2002 , 91, 46–58

Li-June Ming* and Jon D. Epperson

Department of Chemistry and Institute for Biomolecular Science
University of South Florida
4202 Fowler Avenue, SCA400
Tampa, FL 33620-5250

    Bacitracin is a widely used metallopeptide antibiotic produced by Bacillus subtilis and B. licheniformis with a potent bactericidal activity directed primarily against Gram-positive organisms.  This antibiotic requires a divalent metal ion such as Zn2+ for its biological activity, and has been reported to bind several other transition metal ions, including Mn2+, Co2+, Ni2+, and Cu2+ .  Despite the wide use of bacitracin since its discovery in the early 40’s, structure-activity relationship of this drug has not been established and the coordination chemistry of its metal complexes has not been fully determined until recent years.  This antibiotic has been suggested to influence cell functioning through more than one route.  Since bacterial resistance against bacitracin is still scarce despite several decades of wide use, this antibiotic can serve as an ideal lead for design of potent peptidyl antibiotics lacking bacterial resistance.  In this review, the results from physical (including NMR, EPR, and EXAFS) and molecular biological studies regarding the synthesis and structure of bacitracin, the coordination chemistry of its metal derivatives, the mechanism of its antibiotic actions, its influence on membrane function, and its structure and function relationship are discussed.  

reprint of this review article in pdf

A brief account about bacitracin
Abstract and pdf file of our NMR study of Co(II)-bacitracin published in Biochemistry