title: Origins of the β-lactam rings in natural products.
abstract: Naturally occurring β-lactam compounds fall into four basic structural groups, the penicillins/cephalosporins, the clavams, the carbapenems and the monocyclic β-lactams. Biosynthetic studies have clarified the steps involved in the formation of the β-lactam ring for the first three of these groups, but the corresponding process or processes for the monocyclic β-lactams remains obscure. Isopenicillin N synthase is responsible for formation of the β-lactam ring in all penicillin/cephalosporin compounds, and the reaction catalyzed is completely separate from that of β-lactam synthetase, the enzyme responsible for ring formation in all clavam compounds. Conversely, carbapenam synthetase, the enzyme responsible for β-lactam ring formation for all carbapenem compounds, shows clear relatedness to β-lactam synthetase, despite differences in the substrates and the products for the two enzymes. The mechanism of ring formation has not yet been clarified for any of the monocyclic β-lactams, but a third distinct mechanism of β-lactam ring formation seems likely, and this group includes such a diverse collection of structures that even more new ring-forming reactions may be involved.
authors.affiliation: Department of Biology, Memorial University of Newfoundland, St John's, Newfoundland and Labrador, Canada.
authors.forename: Kapil
authors.initials: K
authors.lastname: Tahlan
authors.forename: Susan E
authors.initials: SE
authors.lastname: Jensen
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics*; D019143:Evolution, Molecular; D047090:beta-Lactams / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001688:Biological Products; D047090:beta-Lactams