Systematic (IUPAC) name
4-Hydroxy-3-[4-hydroxy-3-(3-methylbut-2-enyl)benzamido]-8-methylcoumarin-7-yl 3-O-carbamoyl-5,5-di-C-methyl-α-l-lyxofuranoside
Clinical data
AHFS/ International Drug Names
Pregnancy cat.  ?
Legal status  ?
Routes intravenous
Pharmacokinetic data
Bioavailability negligible oral bioavailability
Metabolism excreted unchanged
Half-life 6 hours
Excretion renal
CAS number 303-81-1 YesY
ATC code ?
PubChem CID 9346
DrugBank APRD00694
ChemSpider 10226117 YesY
UNII 17EC19951N YesY
KEGG C05080 N
Chemical data
Formula C31H36N2O11 
Mol. mass 612.624
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

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[1] a member of the order Actinobacteria . Other aminocoumarin antibiotics include clorobiocin and coumermycin A1.[2] Novobiocin was first reported in the mid-1950s (then called streptonivicin).[3][4]


Mechanism of action

The molecular basis of action of novobiocin, and other related drugs clorobiocin and coumermycin A1 has been examined.[2][5][6][7][8] 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. The GyrA subunit is involved in the DNA nicking and ligation activity.


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.[5] 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.[9] The overlap of the coumarin and ATP-binding sites is consistent with aminocoumarins being competitive inhibitors of the ATPase activity.[10]

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.[10]


This aminocoumarin antibiotic consists of three major substituents. The 3-dimethylallyl-4-hydroxybenzoic acid moiety, known as ring A, is derived from prephenate and dimethylallyl pyrophosphate. The aminocoumarin moiety, known as ring B, is derived from L-Tyrosine. The final component of novobiocin is the sugar derivative L-noviose, known as ring C, which is derived from glucose-1-phosphate. The biosynthetic gene cluster for novobiocin was identified by Heide and coworkers in 1999 (published 2000) from Streptomyces spheroides NCIB 11891.[11] They identified 23 putative open reading frames (ORFs) and more than 11 other ORFs that may play a role in novobiocin biosynthesis.

The biosynthesis of ring A (see Fig. 1) begins with prephenate which is a derived from the shikimic acid biosynthetic pathway. The enzyme NovF catalyzes the decarboxylation of prephenate while simultaneously reducing nicotinamide adenine dinucleotide phosphate (NADP+) to produce NADPH. Following this NovQ catalyzes the electrophilic substitution of the phenyl ring with dimethylallyl pyrophosphate (DMAPP) otherwise known as prenylation.[12] DMAPP can come from either the mevalonic acid pathway or the deoxyxylulose biosynthetic pathway. Next the 3-dimethylallyl-4-hydroxybenzoate molecule is subjected to two oxidative decarboxylations by NovR and molecular oxygen.[13] NovR is a non-heme iron oxygenase with a unique bifunctional catalysis. In the first stage both oxygens are incorporated from the molecular oxygen while in the second step only one is incorporated as determined by isotope labeling studies. This completes the formation of ring A.

Figure 1. Biosynthesis of 3-dimethylallyl-4-hydroxybenzoic acid component of novobiocin (ring A)

The biosynthesis of ring B (see Fig. 2) begins with the natural amino acid L-Tyrosine. This is then adenylated and thioesterified onto the peptidyl carrier protein (PCP) of NovH by ATP and NovH itself.[14] NovI then further modifies this PCP bound molecule by oxidizing the β-position using NADPH and molecular oxygen. NovJ and NovK form a heterodimer of J2K2 which is the active form of this benzylic oxygenase.[15] This process uses NADP+ as a hydride acceptor in the oxidation of the β-alcohol. This ketone will prefer to exist in its enol tautomer in solution. Next a still unidentified protein catalyzes the selective oxidation of the benzene (as shown in Fig. 2). Upon oxidation this intermediate will spontaneously lactonize to form the aromatic ring B and lose NovH in the process.

Figure 2. Biosynthesis of 3-amino-4,7-dihydroxy-2H-chromen-2-one component of novobiocin (ring B)

The biosynthesis of L-noviose (ring C) is shown in Fig. 3. This process starts from glucose-1-phosphate where NovV takes dTTP and replaces the phosphate group with a dTDP group. NovT then oxidizes the 4-hydroxy group using NAD+. NovT also accomplishes a dehydroxylation of the 6 position of the sugar. NovW then epimerizes the 3 position of the sugar.[16] The methylation of the 5 position is accomplished by NovU and S-adenosyl methionine (SAM). Finally NovS reduces the 4 position again to achieve epimerization of that position from the starting glucose-1-phosphate using NADH.

Figure 3. Biosynthesis of L-noviose component of novobiocin (ring C)

Rings A, B, and C are coupled together and modified to give the finished novobiocin molecule. Rings A and B are coupled together by the enzyme NovL using ATP to diphosphorylate the carboxylate group of ring A so that the carbonyl can be attacked by the amine group on ring B. The resulting compound is methylated by NovO and SAM prior to glycosylation.[17] NovM adds ring C (L-noviose) to the hydroxyl group derived from tyrosine with the loss of dTDP. Another methylation is accomplished by NovP and SAM at the 4 position of the L-noviose sugar.[18] This methylation allows NovN to carbamylate the 3 position of the sugar as shown in Fig. 4 completing the biosynthesis of novobiocin.

Figure 4. Completed biosynthesis of novobiocin from ring systems A, B, and C

Clinical Use

It is active against Staphylococcus epidermidis and may be used to differentiate it from the other coagulase-negative Staphylococcus saprophyticus, which is resistant to novobiocin, in culture.

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.[19][20] It has since been withdrawn from the market.[21] Novobiocin is effective antistaphylococcal agent used in the treatment of MRSA.[22]


  1. ^ Lanoot B., Vancanneyt M., Cleenwerck I., Wang L., Li W., Liu Z., Swings J. (2002). "The search for synonyms among streptomycetes by with SDS-PAGE of whole-cell proteins. Emendation of the species Streptomyces aurantiacus, Streptomyces cacaoi subsp. cacaoi, Streptomyces caeruleus and Streptomyces violaceus". Int. J. Syst. Evol. Microbiol 52 (Pt 3): 823–829. doi:10.1099/ijs.0.02008-0. PMID 12054245. 
  2. ^ a b Alessandra da Silva Eustáquio (2004) Biosynthesis of aminocoumarin antibiotics in Streptomyces: Generation of structural analogues by genetic engineering and insights into the regulation of antibiotic production. DISSERTATION
  3. ^ Hoeksema H., Johnson J. L., Hinman J. W. (1955). "Structural studies on streptonivicin, a new antibiotic". J Am Chem Soc 77: 6710–6711. 
  4. ^ Smith C. G., Dietz A., Sokolski W. T., Savage G. M. (1956). "Streptonivicin, a new antibiotic. I. Discovery and biologic studies". Anitbiotics & Chemotherapy 6: 135–142. 
  5. ^ a b Maxwell A (1993). "The interaction between coumarin drugs and DNA gyrase". Mol Microbiol 9 (4): 681–686. doi:10.1111/j.1365-2958.1993.tb01728.x. PMID 8231802. 
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  7. ^ Lewis R. J., Tsai F. T. F., Wigley D. B. (1996). "Molecular mechanisms of drug inhibition of DNA gyrase". Bioessays 18 (8): 661–671. doi:10.1002/bies.950180810. PMID 8760340. 
  8. ^ Maxwell A., Lawson D. M. (2003). "The ATP-binding site of type II topoisomerases as a target for antibacterial drugs". Curr Top Med Chem 3 (3): 283–303. doi:10.2174/1568026033452500. PMID 12570764. 
  9. ^ F.T.F. Tsai, O.M. Singh, T.Skarzynski, A.J. Wonacott, S. Weston, A. Tucker, R.A. Pauptit, A.L. Breeze, J.P. Poyser, R. O'Brien et al., The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin. Proteins 28 (1997), pp. 41–52
  10. ^ a b Flatman R.H., Eustaquio A., Li S., Heide L., Maxwell A. (2006). "Structure-Activity Relationships of Aminocoumarin-Type Gyrase and Topoisomerase IV Inhibitors Obtained by Combinatorial Biosynthesis". Antimicrob Agents Chemother 50 (4): 1136–1142. doi:10.1128/AAC.50.4.1136-1142.2006. PMC 1426943. PMID 16569821. 
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  12. ^ Pojer F, Wemakor E, Kammerer B, et al. (March 2003). "CloQ, a prenyltransferase involved in clorobiocin biosynthesis". Proc. Natl. Acad. Sci. U.S.A. 100 (5): 2316–21. Bibcode 2003PNAS..100.2316P. doi:10.1073/pnas.0337708100. PMC 151338. PMID 12618544. 
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  15. ^ Pacholec M, Hillson NJ, Walsh CT (September 2005). "NovJ/NovK catalyze benzylic oxidation of a β-hydroxyl tyrosyl-S-pantetheinyl enzyme during aminocoumarin ring formation in novobiocin biosynthesis". Biochemistry 44 (38): 12819–26. doi:10.1021/bi051297m. PMID 16171397. 
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  21. ^ Albamycin and Novobiocin Sodium - Attorney, Lawsuit, Law Suit, Case, Claim, Settlement, Lawyer, Litigation
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Look at other dictionaries:

  • novobiocin — novobiocin. См. новобиоцин. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) …   Молекулярная биология и генетика. Толковый словарь.

  • novobiocin calcium — the calcium salt of novobiocin, having the same actions as the base; used in the treatment of infections in children due to susceptible bacteria resistant to other antibiotics; administered orally …   Medical dictionary

  • novobiocin sodium — the sodium salt of novobiocin, having the same appearance, actions, uses, and mode of administration as the calcium salt; usually used in adults …   Medical dictionary

  • novobiocin — noun Etymology: novo (perhaps modification of Latin niveus snowy, specific epithet of the bacterium Streptomyces niveus) + bi + mycin Date: 1956 a weak dibasic acid C31H36N2O11 that is highly toxic to humans and is sometimes used as an… …   New Collegiate Dictionary

  • novobiocin — no·vo·bi·o·cin (nō və bīʹə sĭn) n. An antibiotic, C31H36N2O11, produced by the actinomycete Streptomyces nivens and used to treat infections by gram positive bacteria.   [Probably Latin novus, new; see novice + antibiotic + in.] * * * …   Universalium

  • novobiocin — An antibiotic antibacterial substance produced by fermentation from cultures of Streptomyces niveus or S. spheroides, effective against penicillin resistant Staphylococcus and Proteus; also available as n. calcium and n. sodium. SYN:… …   Medical dictionary

  • novobiocin — n. pale yellow crystalline compound derived from ethanol that functions as an antibiotic, crystallinic acid, streptonivicin (Chemistry) …   English contemporary dictionary

  • novobiocin — no·vo·bi·o·cin …   English syllables

  • novobiocin — /noʊvoʊˈbaɪəsən/ (say nohvoh buyuhsuhn) noun an antibiotic similar to streptomycin. {novo (combining form of Latin novus new) + bio + (strepto)mycin} …  

  • novobiocin — An antibiotic drug used to treat infection …   English dictionary of cancer terms

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