Novobiocin

Novobiocin is an aminocoumarin antibiotic that was produced by the actinomycete Streptomyces niveus, which has recently been identified as a subjective synonym for S. spheroides a member of the order Actinobacteria. Other aminocoumarin antibiotics include clorobiocin and coumermycin A1. Novobiocin was first reported in the middle of 1950s (called then streptonivicin).

Mechanism of action
The molecular basis of action of novobiocin, and other related drugs clorobiocin and coumermycin A1 has been examined. Aminocoumarins are very potent inhibitors of bacterial DNA gyrase and work by targeting the GyrB subunit of the enzyme involved in energy tranduction. Novobiocin as well as the other aminocoumarin antibiotics act as competitive inhibitors of the ATPase reaction catalysed by GyrB. The potency of novobiocin is considerably higher than that of the fluoroquinolones that also target DNA gyrase, but at a different site on the enzyme. The GyrA subunit is involved in the DNA nicking and ligation activity.

Structure
Novobiocin is an aromatic ether compound. Novobiocin may be divided up into three entities; a benzoic acid derivative, a coumarin residue, and the sugar novobiose. . X-ray crytallographic studies have found that the drug-receptor complex of Novobiocin and DNA Gyrase shows that ATP and Novobiocin have overlapping binding sites on the gyrase molecule. The overlap of the coumarin and ATP-binding sites is consistent with aminocoumarins being competitive inhibitors of the ATPase activity.

Structure Activity Relationship
In structure activity relationship experiments it was found that removal of the carbamoyl group located on the novobiose sugar lead to a dramatic decrease in inhibitory activity of novobiocin.

Clinical Use
Novobiocin was licenced for clinical use under the tradename Albamycin® (Pharmacia And Upjohn) in the 1960s. Its efficacy has been demonstrated in preclinical and clinical trials. It has since been withdrawn from the market. Novobiocin is effective antistaphylococcal agent used in the treatment of MRSA. It is also active against Staphylococcus epidermidis and may be used to differentiate from the other coagulase-negative Staphylococcus saprophyticus, which is resistant to novobiocin, in culture.