Genome-wide gene expression changes in an industrial clavulanic acid overproduction strain of Streptomyces clavuligerus

Marnix H. Medema, Mohammad T. Alam, Wilbert H.M. Heijne, Marco A. Van Den Berg, Ulrike Müller, Axel Trefzer, Roel A.L. Bovenberg, Rainer Breitling, Eriko Takano

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)300-305
Number of pages6
JournalMicrobial Biotechnology
Volume4
Issue number2
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Applied Microbiology and Biotechnology

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