Clavulanic acid

Clavulanic acid (rINN) /ˌklævjuːˈlænᵻk ˈæsᵻd/ 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.

Sources

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

Clavulanic acid is biosynthetically generated from the amino acid arginine and the sugar glyceraldehyde 3-phosphate.

Biosynthesis

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.