Molecular genetics of carbapenem antibiotic biosynthesis

SJ McGowan, MTG Holden, BW Bycroft, GPC Salmond*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Carbapenems are potent beta-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 beta-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 beta-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.

Original languageEnglish
Pages (from-to)135-141
Number of pages7
JournalAntonie van Leeuwenhoek
Volume75
Issue number1-2
Publication statusPublished - 1999

Keywords

  • beta-lactam antibiotic
  • carbapenem
  • Erwinia carotovora
  • quorum sensing
  • Serratia marcescens
  • thienamycin
  • ERWINIA-CAROTOVORA
  • N-(3-OXOHEXANOYL)-L-HOMOSERINE LACTONE
  • PRODUCTION GENES
  • CLAVULANIC ACID
  • LUX AUTOINDUCER
  • THIENAMYCIN
  • SERRATIA
  • BIOLUMINESCENCE
  • SUPERFAMILY
  • SALMONELLA

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