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Clavulanic acid biosynthesis and genetic manipulation for its overproduction

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Abstract

Clavulanic acid, a β-lactamase inhibitor, is used together with β-lactam antibiotics to create drug mixtures possessing potent antimicrobial activity. In view of the clinical and industrial importance of clavulanic acid, identification of the clavulanic acid biosynthetic pathway and the associated gene cluster(s) in the main producer species, Streptomyces clavuligerus, has been an intriguing research question. Clavulanic acid biosynthesis was revealed to involve an interesting mechanism common to all of the clavam metabolites produced by the organism, but different from that of other β-lactam compounds. Gene clusters involved in clavulanic acid biosynthesis in S. clavuligerus occupy large regions of nucleotide sequence in three loci of its genome. In this review, clavulanic acid biosynthesis and the associated gene clusters are discussed, and clavulanic acid improvement through genetic manipulation is explained.

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  1. School of Biological Sciences, Seoul National University, Seoul, 151-747, South Korea

    Ju Yeon Song & Kye Joon Lee

  2. Korea Research Institute of Bioscience and Biotechnology, 111 Gwahangno, Yuseong-gu, Daejeon, 305-806, South Korea

    Ju Yeon Song

  3. Department of Biological Sciences, University of Alberta, Edmonton, T6G 2E9, Canada

    Susan E. Jensen

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  1. Ju Yeon Song
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  2. Susan E. Jensen
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Song, J.Y., Jensen, S.E. & Lee, K.J. Clavulanic acid biosynthesis and genetic manipulation for its overproduction. Appl Microbiol Biotechnol 88, 659–669 (2010). https://doi.org/10.1007/s00253-010-2801-2

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