Open AccessGenome‐wide gene expression changes in an industrial clavulanic acid overproduction strain of Streptomyces clavuligerus
Author(s) -
Medema Marnix H.,
Alam Mohammad T.,
Heijne Wilbert H. M.,
van den Berg Marco A.,
Müller Ulrike,
Trefzer Axel,
Bovenberg Roel A. L.,
Breitling Rainer,
Takano Eriko
Publication year - 2011
Publication title -
microbial biotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.287
H-Index - 74
ISSN - 1751-7915
DOI - 10.1111/j.1751-7915.2010.00226.x
Subject(s) - streptomyces clavuligerus , clavulanic acid , gene , mutagenesis , biology , streptomyces , metabolic engineering , genome , overproduction , strain (injury) , genetics , regulator gene , biochemistry , computational biology , regulation of gene expression , bacteria , mutation , antibiotics , actinomycetales , amoxicillin , anatomy
Summary 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.