Aminocoumarin

 Aminocoumarin  is a class of antibiotics which act by an inhibition of the DNA Gyrase enzyme involved in the cell division in bacteria. They are derived from  Streptomyces  species, whose most well-known representative  Streptomyces coelicolor  was completely sequenced in 2002. The Aminocoumarin antibiotics include


 * Novobiocin, Albamycin® (Pharmacia And Upjohn)
 * Coumermycin
 * Clorobiocin

Mechanism of action
The  Aminocoumarin  antibiotics are known inhibitors of DNA gyrase. Antibiotics of the aminocoumarin family exert their therapeutic activity by binding tightly to the B subunit of bacterial DNA gyrase, thereby inhibiting this essential enzyme. They compete with ATP for binding to the B subunit of this enzyme and inhibit the ATP-dependent DNA supercoiling catalysed by gyrase. X-ray crystallography studies have confirmed binding at the ATP-binding site located on the gyrB subunit of DNA gyrase.

Structure
The core of aminocoumarin antibiotics is made up of a 3-Amino-4,7-dihydroxycumarin ring, which is linked e.g. with a sugar in 7-Position and a benzoic acid derivative in 3-Position.

Clorobiocin is a natural antibiotic isolated from several Streptomyces strains and differs from novobiocin in that the methyl group at the 8 position in the coumarin ring of novobiocin is replaced by a chlorine atom, and the carbamoyl at the 3' position of the noviose sugar is substituted by a 5-methyl-2-pyrrolylcarbonyl group.

Clinical use
The clinical use of these antibiotic class has been restricted due to their low water solubility, low activity against gram-negative bacteria and toxiciy in vivo.