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Molecular genetics of carbapenem antibiotic biosynthesis

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Abstract

Carbapenems are potent β-lactam antibiotics with a broad spectrum of activity against both Gram positive and Gram negative bacteria. As naturally produced metabolites, they have been isolated from species of Streptomyces, Erwinia and Serratia. The latter two members of the Enterobacteriaceae have proved to be genetically amenable and a growing body of research on these organisms now exists concerning the genes responsible for carbapenem biosynthesis and the regulatory mechanisms controlling their expression. A cluster of nine carbapenem (car) genes has been identified on the chromosome of Erwinia carotovora. These genes encode the enzymes required for construction of carbapenem and the proteins responsible for a novel β-lactam resistance mechanism, conferring carbapenem immunity in the producing host. Although sharing no homology with the well known enzymes of penicillin biosynthesis, two of the encoded proteins are apparently similar to enzymes of the clavulanic acid biosynthetic pathway implying a common mechanism for construction of the β-lactam ring. In addition, a transcriptional activator is encoded as the first gene of the carbapenem cluster and this allows positive expression of the remaining downstream genes in response to a quorum sensing, N-acyl homoserine lactone, signalling molecule.

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Authors and Affiliations

  1. Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK

    Simon J. McGowan & George P. C. Salmond

  2. Department of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK

    Matthew T. G. Holden & Barrie W. Bycroft

Authors
  1. Simon J. McGowan
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  2. Matthew T. G. Holden
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  3. Barrie W. Bycroft
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  4. George P. C. Salmond
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Correspondence to George P. C. Salmond.

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McGowan, S.J., Holden, M.T.G., Bycroft, B.W. et al. Molecular genetics of carbapenem antibiotic biosynthesis. Antonie Van Leeuwenhoek 75, 135–141 (1999). https://doi.org/10.1023/A:1001768428383

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