7-Aminocephalosporanic acid(7-ACA) is the core chemical structure for the synthesis of cephalosporin antibiotics, is a potent β-lactamase inhibitor[1]. The N-phenylacetyl derivative of 7-aminocephalosporanic acid (cephaloram) had roughly the same activity as benzylpenicillin against a number of Gram-positive organisms and about one-eighth of the activity of benzylpenicillin against penicillinsensitive strains of Staphylococcus aureus. This derivative and the N-alpha-phenoxypropionyl derivative of 7-aminocephalosporanic acid were 4 to 8 and 4 to 16 times as active as methicillin against penicillinase- and nonpenicillinase-producing staphylococcal strains, respectively. After forty-eight subcultures in the presence of antibiotic the increase in minimum inhibitory concentration against the staphylococcus was about four-times as great for cephaloram as for cephalosporin C. The resistant penicillinase-producing strains remained stable after six subcultures in antibiotic-free medium, and all the strains retained coagulase activity[2]. 7-ACA is produced from cephalosporin C via glutaryl-7-ACA (GL-7-ACA) by a bioconversion process using d-amino acid oxidase and cephalosporin acylase (or GL-7-ACA acylase). The best mutant enzyme for catalytic efficiency, with a k(cat)/K(m) value for GL-7-ACA almost 50-fold higher than that of the D433N enzyme, has three amino acid substitutions: D433N, Y444A, and G484A[3].
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