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Genome-wide gene expression changes in an industrial clavulanic acid overproduction strain of Streptomyces clavuligerus
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Medema, Marnix H, Alam, Mohammad T., Heijne, Wilbert H M, Van den Berg, Marco, Müller, Ulrike, Trefzer, Axel, Bovenberg, Roel A L, Breitling, Rainer and Takano, Eriko (2010) Genome-wide gene expression changes in an industrial clavulanic acid overproduction strain of Streptomyces clavuligerus. Microbial Biotechnology, 4 (2). pp. 300-5. doi:10.1111/j.1751-7915.2010.00226.x ISSN 1751-7907.
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Official URL: http://dx.doi.org/10.1111/j.1751-7915.2010.00226.x
Abstract
To increase production of the important pharmaceutical compound clavulanic acid, a β-lactamase inhibitor, both random mutagenesis approaches and rational engineering of Streptomyces clavuligerus strains have been extensively applied. Here, for the first time, we compared genome-wide gene expression of an industrial S. clavuligerus strain, obtained through iterative mutagenesis, with that of the wild-type strain. Intriguingly, we found that the majority of the changes contributed not to a complex rewiring of primary metabolism but consisted of a simple upregulation of various antibiotic biosynthesis gene clusters. A few additional transcriptional changes in primary metabolism at key points seem to divert metabolic fluxes to the biosynthetic precursors for clavulanic acid. In general, the observed changes largely coincide with genes that have been targeted by rational engineering in recent years, yet the presence of a number of previously unexplored genes clearly demonstrates that functional genomic analysis can provide new leads for strain improvement in biotechnology.
| Item Type: | Journal Article | ||||||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Microbial Biotechnology | ||||||||
| Publisher: | Wiley-Blackwell Publishing Ltd. | ||||||||
| ISSN: | 1751-7907 | ||||||||
| Official Date: | 2 November 2010 | ||||||||
| Dates: |
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| Volume: | 4 | ||||||||
| Number: | 2 | ||||||||
| Page Range: | pp. 300-5 | ||||||||
| DOI: | 10.1111/j.1751-7915.2010.00226.x | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access |
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