The enzymes of beta-lactam biosynthesis

The beta-lactam antibiotics and related beta-lactamase inhibitors are amongst the most important small molecules in clinical use. Most, but not all, beta-lactams including penicillins, cephalosporins, and clavulanic acid are produced via fermentation or via modification of fermented intermediates, with important exceptions being the carbapenems and aztreonam. The desire for more efficient routes to existing antibiotics and for access to new and synthetically challenging ones stimulates continued interest in beta-lactam biosynthesis. We review knowledge of the pathways leading to beta-lactam antibiotics focusing on the mechanisms, structures and biocatalytic applications of the enzymes involved.