Journal of Microbiology and Biotechnology

  • 제17권9호
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  • Pages.1538-1545
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  • 2007
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  • 1017-7825(pISSN)
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  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
권호 표지

Enhancement of Clavulanic Acid by Replicative and Integrative Expression of ccaR and cas2 in Streptomyces clavuligerus NRRL3585

  • Hung, Trinh Viet (Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction (IBR), Sun Moon University) ;
  • Malla, Sailesh (Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction (IBR), Sun Moon University) ;
  • Park, Byoung-Chul (Korea Research Institute of Bioscience and Biotechnology) ;
  • Liou, Kwang-Kyoung (Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction (IBR), Sun Moon University) ;
  • Lee, Hei-Chan (Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction (IBR), Sun Moon University) ;
  • Sohng, Jae-Kyung (Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction (IBR), Sun Moon University)
  • 발행 : 2007.09.30
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초록

Clavulanic acid (CA) is an inhibitor of ${\beta}$-lactamase that is produced from Streptomyces clavuligerus NRRL3585 and is used in combination with other antibiotics in clinical treatments. In order to increase the production of CA, the replicative and integrative expressions of ccaR (encoding for a specific regulator of the CA biosynthetic operon) and cas2 (encoding for the rate-limiting enzyme in the CA biosynthetic pathway) were applied. Six recombinant plasmids were designed for this study. The pIBRHL1, pIBRHL3, and pIBRHL13 were constructed for overexpression, whereas pNQ3, pNQ2, and pNQ1 were constructed for chromosomal integration with ccaR, cas2, and ccaR-cas2, respectively. All of these plasmids were transformed into S. clavuligerus NRRL3585. CA production in transformants resulted in a significantly enhanced amount greater than that of the wild type, a 2.25-fold increase with pIBRHLl, a 9.28-fold increase with pNQ3, a 5.06-fold increase with pIBRHL3, a 2.93-fold increase with pNQ2 integration, a 5.79-fold increase with pIBRHLl3, and a 23.8-fold increase with pNQ1. The integrative pNQl strain has been successfully applied to enhance production.

키워드

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