CHAPTER 8 – Beta-Lactams

Publisher Summary This chapter reviews the biochemistry, genetics, and regulation of β-lactam antibiotics. Penicillins, cephalosporins, and cephamycins are related biosynthetically; they arise from branches and variations of a basic pathway that draws upon three component amino acids, L-a-aminoadipic acid, L-cysteine, and L-valine. The three amino acids can be considered the interface between pathways of primary and secondary metabolism. The first enzyme in the conversion of lysine to α-aminoadipate, is clustered with other genes encoding enzymes of β-lactam biosynthesis in Streptomyces clavuligerus and Nocardia lactamdurans. Cephamycin biosynthesis is studied in detail in S. clavuligerus, the organism is best known and commercially used for production of the atypical β -lactam, clavulanic acid. This clavam has a bicyclic ring structure resembling that of penicillin, except that oxygen replaces sulfur in the five-membered ring. It is used clinically in combination with β-lactamase-sensitive antibiotics to combat infections that would be resistant to the β-lactam antibiotic alone. The monobactams are a diverse group of compounds with the basic structure represented by sulfazecin.