Innovations in cephalosporin and penicillin production : Painting the antibiotics industry green

Because of the long lifetime of β-lactam antibiotics it appears to be attractive to invest in the development of new routes to these compounds. In ths review an overview is given on the routes to 6-aminopenicillanic acid (6-APA), 7-amino- desacetoxycephalosporanic acid (7-ADCA), semi-synthetic penicillins (SSP's) and semi- synthetic cephalosporins (SSP's). It will be shown that with the usage of biocatalysis and fermentation several breakthroughs have been obtained. With enzyme catalyzed reactions it appeared to be possible to directly remove and add sidechains to the β-lactam nucleus. Without the enzyme several protecting steps are required to perform these conversions. With the aid of genetic engineering it is now possible to construct an effective pathway towards the 7-ADCA structure within the producing organism. These new processes result in shorter and more cost-effective routes to the endproduct while being highly advantageous from an environmental perspective.