Regulation and biosynthesis of carbapenem antibiotics in bacteria

Carbapenem antibiotics are members of the beta-lactam family of antibiotics, the most important class of antibiotics currently in clinical use. They are active against many important Gram-positive and Gram-negative pathogens. One important feature of carbapenem antibiotics is their resistance to several beta-lactamases. Thienamycin, isolated from Streptomyces cattleya, was the first carbapenem described. Other well-studied carbapenems were isolated from the Gram-negative bacteria Erwinia carotovora subsp. carotovora, Serratia sp. strain ATCC39006 and Photorhabdus luminescens strain TT01. Here, we review the genetics and biochemistry of carbapenem production in these bacteria. Research into carbapenems could uncover a new repertoire of bioactive molecules and biosynthetic enzymes, and exploiting these novel enzymes could lead to development of new classes of antibiotics with useful chemotherapeutic activities.