Aminocoumarin is a class of antibiotics that act by an inhibition of the DNA gyrase enzyme involved in the cell division in bacteria. They are derived from Streptomyces species,[1] whose best-known representative – Streptomyces coelicolor – was completely sequenced in 2002.[2] The aminocoumarin antibiotics include:[3]
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.[citation needed]
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.[4]
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.[5] They compete with ATP for binding to the B subunit of this enzyme and inhibit the ATP-dependent DNA supercoiling catalysed by gyrase.[6] X-ray crystallography studies have confirmed binding at the ATP-binding site located on the gyrB subunit of DNA gyrase.[4] Their affinity for gyrase is considerably higher than that of modern fluoroquinolones, which also target DNA gyrase but at the gyrA subunit.[7]
Resistance to this class of antibiotics usually results from genetic mutation in the gyrB subunit.[8] Other mechanisms include de novo synthesis of a coumarin-resistant gyrase B subunit by the novobiocin producer S. sphaeroides .[7]
The clinical use of this antibiotic class has been restricted due to the low water solubility, low activity against gram-negative bacteria,[6] and toxicity in vivo of this class of antibiotics.[9]
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| Antifolates (inhibit bacterial purine metabolism, thereby inhibiting DNA and RNA synthesis) |
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| Quinolones (inhibit bacterial topoisomerase and/or DNA gyrase, thereby inhibiting DNA replication) |
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| Anaerobic DNA inhibitors |
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| RNA synthesis |
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