Genes for the biosynthesis of beta-lactam compounds in microorganisms

Rapid progress has recently been made in the characterization of genes and gene clusters involved in the biosynthesis of beta-lactam antibiotics such as penicillins, cephalosporins and cephamycins. The biosynthetic pathways are found in a wide range of microorganisms, including fungi, actinomycetes and Gram-negative bacteria. Comparisons of gene sequences (particularly the genes encoding isopenicillin N synthetase) and gene organization in these different microorganisms have led to proposals about the evolution of this group of pathways, and how they might have been transferred from prokaryotes to eukaryotes. The isolation and characterization of the genes encoding ACV (tripeptide) synthetase, the first step in the beta-lactam biosynthetic pathway, have revealed the presence of three partly repeated domains, most likely responsible for the recognition, adenylation and activation of the three amino acid precursors of the penams and cephems. This has confirmed their classification as peptide synthetases, distantly related to enzymes responsible for the synthesis of peptide antibiotics in Bacillus brevis and other bacteria and fungi.