Removal of the fermentation by‐product succinyl L ‐tyrosine from the β‐lactamase inhibitor clavulanic acid using a molecularly imprinted polymer

Clavulanic acid is a β–lactamase inhibitor used in therapeutic combinations with the penicillin‐type antibiotics. During the fermentation leading to clavulanic acid, a succinyl L ‐tyrosine by‐product is unavoidably formed. Occasionally, the amount of this by‐product is found to be as high as 2% of the product even after standard purification operations. To further remove this impurity, we prepared a highly specific adsorbent for succinyl L ‐tyrosine with the molecular imprinting technique. This was performed by simultaneously using vinylbenzyl trimethylammonium chloride and methacrylic acid as the functional monomers. The imprinted polymer selectively bound succinyl L ‐tyrosine, and could be successfully used to remove this impurity at concentrations of less than 2% in the presence of clavulanic acid. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 23–28, 2002.