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The Journal of Antibiotics (2013) 66, 401410
& 2013 Japan Antibiotics Research Association All rights reserved 0021-8820/13 http://www.nature.com/ja
Web End =www.nature.com/ja
Kapil Tahlan1 and Susan E Jensen2
Naturally occurring b-lactam compounds fall into four basic structural groups, the penicillins/cephalosporins, the clavams,the carbapenems and the monocyclic b-lactams. Biosynthetic studies have claried the steps involved in the formation of the b-lactam ring for the rst three of these groups, but the corresponding process or processes for the monocyclic b-lactams remains obscure. Isopenicillin N synthase is responsible for formation of the b-lactam ring in all penicillin/cephalosporin compounds, and the reaction catalyzed is completely separate from that of b-lactam synthetase, the enzyme responsible for ring formation in all clavam compounds. Conversely, carbapenam synthetase, the enzyme responsible for b-lactam ring formation for all carbapenem compounds, shows clear relatedness to b-lactam synthetase, despite differences in the substrates and the products for the two enzymes. The mechanism of ring formation has not yet been claried for any of the monocyclic b-lactams, but a third distinct mechanism of b-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.
The Journal of Antibiotics (2013) 66, 401410; doi:http://dx.doi.org/10.1038/ja.2013.24
Web End =10.1038/ja.2013.24; published online 27 March 2013
Keywords: carbapenem; cephalosporin; monobactam; nocardicin; penicillin; tabtoxin
INTRODUCTION
The b-lactam class of compounds is arguably the most important family of microbial natural products ever applied to human medicine.With the discovery of penicillin early in the twentieth century, treatment of infectious diseases entered the modern era in which antibiotics control and eliminate infections that would otherwise be intractable. Even now when our reliance upon antibiotics is threatened by the ever-increasing threat of antibiotic resistance, the b-lactam class of compounds accounts for 450% of all antibiotic prescriptions.1
Although penicillin was the rst b-lactam compound discovered, we now recognize a whole family of natural products, unied by their possession of the distinctive four-membered b-lactam ring. Biosynthetic studies have shown that the b-lactam class of natural products can be divided into at least four different subgroups based on the origin of the b-lactam ring. These groups will be referred to as the penicillin/cephalosporin, the clavam, the carbapenem and the mono-cyclic b-lactam compounds. Representative structures encompassed by these groupings...