title: Genome-wide gene expression changes in an industrial clavulanic acid overproduction strain of Streptomyces clavuligerus.
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.
authors.affiliation: Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, The Netherlands.
authors.forename: Marnix H
authors.initials: MH
authors.lastname: Medema
authors.forename: Mohammad T
authors.initials: MT
authors.lastname: Alam
authors.forename: Wilbert H M
authors.initials: WH
authors.lastname: Heijne
authors.forename: Marco A
authors.initials: MA
authors.lastname: van den Berg
authors.forename: Ulrike
authors.initials: U
authors.lastname: Müller
authors.forename: Axel
authors.initials: A
authors.lastname: Trefzer
authors.forename: Roel A L
authors.initials: RA
authors.lastname: Bovenberg
authors.forename: Rainer
authors.initials: R
authors.lastname: Breitling
authors.forename: Eriko
authors.initials: E
authors.lastname: Takano
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D019818:Clavulanic Acid / Q000096:biosynthesis*; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D007218:Industrial Microbiology; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D019818:Clavulanic Acid