Department of Biology, Memorial University of Newfoundland, St John's, Newfoundland and Labrador, Canada.
J Antibiot (Tokyo). 2013 Jul;66(7):401-10. doi: 10.1038/ja.2013.24. Epub 2013 Mar 27.
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.
天然存在的β-内酰胺化合物可分为四大基本结构群：青霉素/头孢菌素类、克拉维酸类、碳青霉烯类和单环β-内酰胺类。生物合成研究阐明了前三种结构群β-内酰胺环形成的步骤，但单环β-内酰胺类相应的过程仍然不清楚。异青霉素 N 合酶负责所有青霉素/头孢菌素类化合物中β-内酰胺环的形成，而催化的反应与β-内酰胺合成酶完全不同，β-内酰胺合成酶是负责所有克拉维酸类化合物中环形成的酶。相反，碳青霉烯合成酶是负责所有碳青霉烯类化合物中β-内酰胺环形成的酶，尽管两种酶的底物和产物不同，但与β-内酰胺合成酶有明显的相关性。目前还没有阐明任何单环β-内酰胺的环形成机制，但似乎存在第三种不同的β-内酰胺环形成机制，而且这一类包括如此多样化的结构，甚至可能涉及更多新的环形成反应。
