Clavulanic acid biosynthesis

Clavulanic acid

Clinical data
Pronunciation	/ˌklævjuːˈlænɪk ˈæsɪd/
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: B1 US: B (No risk in non-human studies)
Routes of administration	Oral, IV
ATC code	J01CR (WHO) (combinations with penicillins)
Legal status
Legal status	AU: S4 (Prescription only) In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	"well absorbed"
Metabolism	hepatic (extensive)
Biological half-life	1 hour
Excretion	renal (30–40%)
Identifiers
IUPAC name (2R,5R,Z)-3-(2-Hydroxyethylidene)-7-oxo-4-oxa-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid
CAS Number	58001-44-8 Y
PubChem CID	5280980
DrugBank	DB00766 Y
ChemSpider	4444466 Y
UNII	23521W1S24
KEGG	D07711 Y
ChEBI	CHEBI:48947 Y
ChEMBL	CHEMBL777 Y
ECHA InfoCard	100.055.500
Chemical and physical data
Formula	C8H9NO5
Molar mass	199.16 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C2N1[C@H](C(/O[C@@H]1C2)=C/CO)C(=O)O
InChI InChI=1S/C8H9NO5/c10-2-1-4-7(8(12)13)9-5(11)3-6(9)14-4/h1,6-7,10H,2-3H2,(H,12,13)/b4-1-/t6-,7-/m1/s1 Y Key:HZZVJAQRINQKSD-PBFISZAISA-N Y

Clavulanic acid (/ˌklævjəˈlænɪk/) is a β-lactam drug that functions as a mechanism-based β-lactamase inhibitor. While not effective by itself as an antibiotic, when combined with penicillin-group antibiotics, it can overcome antibiotic resistance in bacteria that secrete β-lactamase, which otherwise inactivates most penicillins.

In its most common form, the potassium salt potassium clavulanate is combined with:

Clavulanic acid is an example of a clavam.

Clavulanic acid was patented in 1974.

For the treatment of pyelonephritis during pregnancy, and for the treatment of pyelonephritis caused by gram-positive organisms, amoxicillin or amoxicillin-clavulanate potassium is preferred.

The name is derived from strains of Streptomyces clavuligerus, which produces clavulanic acid.

Clavulanic acid is biosynthesized from the amino acid arginine and the sugar glyceraldehyde 3-phosphate. With the β-lactam like structure, clavulanic acid looks structurally similar to penicillin, but the biosynthesis of this molecule involves a different pathway and set of enzymes. Clavulanic acid is biosynthesized by the bacterium Streptomyces clavuligerus, using glyceraldehyde-3-phosphate and L-arginine as the starting materials of the pathway. Although all of the intermediates of the pathway are known, the exact mechanism of each enzymatic reaction is not fully understood. The biosynthesis mainly involves 3 enzymes: clavaminate synthase, β-lactam synthetase and N²-(2-carboxyethyl)-L-arginine synthase(CEA).Clavaminate synthase is a non-heme iron α-keto-glutarate dependent oxygenase that is encoded by orf5 of the clavulanic acid gene cluster. The specific mechanism of how this enzyme works is not fully understood, but this enzyme regulates 3 steps in the overall synthesis of clavulanic acid. All 3 steps occur in the same region of the catalytic iron center, yet do not occur in-sequence and affect different areas of the clavulanic acid structure.