The beta-lactam antibiotics are among the foremost chemotherapeutic agents in combatting bacterial infections in man. As a group they constitute more than 10% of ethical drug sales world-wide. Growing chemical and genetic information suggests that they can be divided into at least four biosynthetic classes. These groups present distinct and intriguing enzymatic solutions to the in vivo task of providing strained ring systems of high chemical potential and inhibitory specificity. Biosynthetic investigations are outlined relying on chemical, enzymatic and genetic methods to understand (1) monocyclic beta-lactam formation evident in the nocardicins and monobactams, (2) genesis of the important beta-lactamase inhibitor clavulanic acid and the related, antipodal clavams and, (3) creation of the carbapenem nucleus using carbapenem-3-carboxylate, the simplest member a family of more than 40 natural products, as the experimental system. While questions of fundamental interest in bioorganic chemistry will be addressed in these studies, valuable knowledge can be gained that lead to improved production of these important commodities, for example, through the incorporation of multiple copies of key biosynthetic genes in commercial fermentation strains, the possible use of immobilized enzymes or their site-specific mutants in synthesis or modification, and the development of improved structural types conferring antiobiotic activity against resistant bacterial strains.
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