Novobiocin, also known as albamycin, is an aminocoumarin antibiotic that is produced by the actinomycete Streptomyces niveus, which has recently been identified as a subjective synonym for S. spheroides[1] a member of the class Actinomycetia.

[7] A combination product of novobiocin and tetracycline, sold by Upjohn under brand names such as Panalba and Albamycin-T, was in particular the subject of intense FDA scrutiny before it was finally taken off the market.

[2][11][12][13][14] Aminocoumarins are very potent inhibitors of bacterial DNA gyrase and work by targeting the GyrB subunit of the enzyme involved in energy transduction.

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.

[citation needed] Novobiocin has been shown to weakly inhibit the C-terminus of the eukaryotic Hsp90 protein (high micromolar IC50).

[16][17] The ATP binding pocket of polymerase theta is blocked by novobiocin resulting in a loss of ATPase activity.

This results in the loss of microhomology-mediated end joining as a pathway for homologous recombination deficient cells to circumvent DNA damaging agents.

The action of novobiocin is syngeristic with PARP inhibitors for reducing tumor size in a mouse model.

Novobiocin may be divided up into three entities; a benzoic acid derivative, a coumarin residue, and the sugar novobiose.

[19] The overlap of the coumarin and ATP-binding sites is consistent with aminocoumarins being competitive inhibitors of the ATPase activity.

The biosynthetic gene cluster for novobiocin was identified by Heide and coworkers in 1999 (published 2000) from Streptomyces spheroides NCIB 11891.

The enzyme NovF catalyzes the decarboxylation of prephenate while simultaneously reducing nicotinamide adenine dinucleotide phosphate (NADP+) to produce NADPH.