Genome-wide gene expression changes in an industrial clavulanic acid overproduction strain of Streptomyces clavuligerus.
Bottom Line: 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.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.
Affiliation: Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, The Netherlands.Show MeSH
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Mentions: Additionally, the clavams gene cluster (cvm1245 and cas1) and the ‘paralogous’ alanylclavam cluster (orfABCD and ceaS1/pah1/bls1/oat1) are significantly overexpressed (Fig. 1), as is the two‐component system involving Cvm7p (SCLAV_p1079‐p1080) that induces expression of the alanylclavam cluster (Tahlan et al., 2007). This suggests the presence of a regulatory mechanism common to all these clusters. CcaR is an unlikely candidate for such a common regulatory factor, as it does not appear to control the paralogous cluster (Tahlan et al., 2004); the pleiotropic regulator AdpA (SCLAV_1957) is a more likely candidate, as it is known to induce clavulanic acid expression (Lopez‐García et al., 2010) and its gene is transcribed almost 2.5 times stronger in DS48802.
Affiliation: Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, The Netherlands.