Recent advances in the biosynthesis of penicillins, cephalosporins and clavams and its regulation

The beta-lactam antibiotics have been serving mankind for over 70 years. Despite this old age, they continue to provide health to the world population by virtue of industrial production and discoveries of new secondary metabolite molecules with useful activities. Sales of these remarkable compounds have reached over $20 billion dollars per year. They include penicillins, cephalosporins, cefoxitin, monobactams, clavulanic acid and carbapenems. Strain improvement of the penicillin-producing species of Penicillium has been truly remarkable, with present strains producing about 100,000 times more penicillin that the original Penicillium notatum of Alexander Fleming. A tremendous amount of information has been gathered on the biosynthetic enzymes involved, the pathways of biosynthesis of beta-lactams as well as their regulation, and the genomics and proteomics of the producing organisms. Modern aspects of the processes are discussed in the present review including genetics, molecular biology, metabolic engineering, genomics and proteomics.