Towards biocatalytic synthesis of beta-lactam antibiotics

This review describes the remarkable transition in the manufacture of beta -lactam antibiotics, which is driven by the desire to reduce or eliminate t he production of waste and the dependence on organic solvents. To this effe ct, traditional chemical procedures are gradually being replaced by biotran sformations. The beta -lactam antibiotics industry has led the way in the i ntroduction of biocatalysis in the fine chemicals industry by replacing the chemical multi-step process for the penicillin nucleus 6-aminopenicillanic acid (6-APA) by an enzymatic one in the early 1990's. Recently, bioprocess es have been developed for the synthesis of the cephalosporin nucleus, 7-am inodeacetoxycephalosporanic acid (7-ADCA) from a penicillin precursor and w ill shortly be commercialized. Thirty years of research have now resulted i n viable enzymatic procedures for coupling the beta -lactam nuclei With D-p henylglycine side-chains. The necessary adaptations in the synthesis of the side-chain donors have likewise resulted in more efficient procedures.