Aminocoumarin is a class of

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

that act by an inhibition of the

DNA gyrase DNA gyrase, or simply gyrase, is an enzyme within the class of topoisomerase and is a subclass of Type II topoisomerases that reduces topological strain in an ATP dependent manner while double-stranded DNA is being unwound by elongating RNA-po ...

enzyme involved in the cell division in

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

. They are derived from ''

Streptomyces ''Streptomyces'', from στρεπτός (''streptós''), meaning "twisted", and μύκης (''múkés''), meaning "fungus", is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of ''St ...

'' species, whose best-known representative – ''

Streptomyces coelicolor ''Streptomyces albidoflavus'' is a bacterium species from the genus of ''Streptomyces'' which has been isolated from soil from Poland. ''Streptomyces albidoflavus'' produces dibutyl phthalate and streptothricins. Small noncoding RNA Bacteri ...

'' – was completely

sequenced In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succi ...

in 2002. The aminocoumarin antibiotics include: *

Novobiocin 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'' a member of the class Actinomycet ...

, Albamycin (

Pharmacia Pharmacia was a pharmaceutical and biotechnological company in Sweden that merged with the American pharmaceutical company Upjohn in 1995. History Pharmacia company was founded in 1911 in Stockholm, Sweden by pharmacist Gustav Felix Grönfel ...

And

Upjohn The Upjohn Company was an American pharmaceutical manufacturing firm (est. 1886) in Hastings, Michigan, by Dr. William E. Upjohn, an 1875 graduate of the University of Michigan medical school. The company was originally formed to make ''friable ...

) * Coumermycin * Clorobiocin

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 ''

'' strains and differs from

novobiocin 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'' a member of the class Actinomycet ...

in that the methyl group at the 8 position in the coumarin ring of

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.

Mechanism of action

The aminocoumarin antibiotics are known inhibitors of

Antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

s of the aminocoumarin family exert their therapeutic activity by binding tightly to the B subunit of bacterial

, 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

. Their

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for gyrase is considerably higher than that of modern

fluoroquinolones Quinolone antibiotics constitute a large group of broad-spectrum antibiotic, broad-spectrum bacteriocidals that share a bicyclic molecule, bicyclic core structure related to the substance 4-Quinolone, 4-quinolone. They are used in human and ve ...

, which also target DNA gyrase but at the gyrA subunit.

Resistance

Resistance to this class of antibiotics usually results from genetic mutation in the gyrB subunit. Other mechanisms include de novo synthesis of a coumarin-resistant gyrase B subunit by the novobiocin producer ''S. sphaeroides ''.

Clinical use

The clinical use of this antibiotic class has been restricted due to the low water solubility, low activity against gram-negative bacteria, and toxicity ''in vivo'' of this class of antibiotics.A. Maxwell, The interaction between coumarin drugs and DNA gyrase. ''Mol. Microbiol''. 9 (1993), pp. 681–686.

References

{{Nucleic acid inhibitors Antibiotics Coumarin drugs