Aminocoumarin is a class of antibiotics that act by an inhibition of the DNA Gyrase

DNA gyrase

DNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-stranded DNA is being unwound by helicase. This causes negative supercoiling of the DNA...

 enzyme involved in the cell division in bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

. They are derived from Streptomyces

Streptomyces

Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...

  species, whose best-known representative - Streptomyces coelicolor

Streptomyces coelicolor

Streptomyces coelicolor is a soil-dwelling Gram-positive bacterium that belongs to the genus Streptomyces.-Usage in biotechnology:Strains of S. coelicolor produce various antibiotics, including actinorhodin, methylenomycin, undecylprodigiosin, and perimycin. Certain strains of S. coelicolor can...

- was completely sequenced in 2002.
The Aminocoumarin antibiotics include:

• Novobiocin
  Novobiocin
  Novobiocin, also known as albamycin or cathomycin, 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 order Actinobacteria . Other aminocoumarin antibiotics include...
  
  , Albamycin (Pharmacia
  Pharmacia
  Pharmacia was a pharmaceutical and biotechnological company in Sweden.-History:Pharmacia was founded in 1911 in Stockholm, Sweden by pharmacist Gustav Felix Grönfeldt at the Elgen Pharmacy. The company is named after the Greek word φαρμακεία, transliterated pharmakeia, which means 'sorcery'...
  
   And Upjohn
  Upjohn
  The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Kalamazoo, Michigan by Dr. William E. Upjohn, an 1875 graduate of the University of Michigan medical school. The company was originally formed to make friable pills, which were specifically designed to be easily digested...
  
  )
• Coumermycin
• Clorobiocin
  Clorobiocin
  Clorobiocin is an aminocoumarin....
  
  

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

Streptomyces

Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...

strains and differs from novobiocin

Novobiocin

Novobiocin, also known as albamycin or cathomycin, 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 order Actinobacteria . Other aminocoumarin antibiotics include...

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

Novobiocin

Novobiocin, also known as albamycin or cathomycin, 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 order Actinobacteria . Other aminocoumarin antibiotics include...

 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 DNA gyrase

DNA gyrase

DNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-stranded DNA is being unwound by helicase. This causes negative supercoiling of the DNA...

. Antibiotic

Antibiotic

An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

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

DNA gyrase

DNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-stranded DNA is being unwound by helicase. This causes negative supercoiling of the DNA...

, 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

DNA gyrase

DNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-stranded DNA is being unwound by helicase. This causes negative supercoiling of the DNA...

.. Their affinity for gyrase is considerably higher than that of modern fluoroquinolones

Quinolone

The quinolones are a family of synthetic broad-spectrum antibiotics. The term quinolone refers to potent synthetic chemotherapeutic antibacterials....

, 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 toxiciy in vivo of this class of antibiotics.