Examination of the regulatory cascade leading to clavulanic acid production in Streptomyces clavuligerus

Ferguson, Nicole L. (2014) Examination of the regulatory cascade leading to clavulanic acid production in Streptomyces clavuligerus. Masters thesis, Memorial University of Newfoundland.

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Abstract

The soil bacterium Streptomyces clavuligerus is important from a pharmacological and commercial standpoint because it is capable of producing many known secondary metabolites, including the potent β-lactamase inhibitor clavulanic acid (CA). This research sought to elucidate unknown aspects of the regulation of CA production in S. clavuligerus via an iTRAQ®-based proteomic study comparing the CA producing wild-type strain and two bald mutants, one of which is defective in both CA production and normal development (ΔbldG) and one which is defective only in normal development (ΔbldA). A total of 33.5% of the entire S. clavuligerus proteome was covered, including 10 sigma factors and over 200 regulators and hypothetical regulators. Many of the regulatory elements were differentially expressed among the strains and several are putatively regulated by the pleiotropic regulator BldG. This study represents the most complete proteomic analysis of S. clavuligerus to date and the only such analysis of a CA producing and a non-producing strain. The protein expression data can serve as a useful tool to direct future research into additional aspects of CA biosynthesis and secondary metabolism.

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