Proteomics analysis of global regulatory cascades involved in clavulanic acid production and morphological development in Streptomyces clavuligerus

  • Nicole L. Ferguson
  • Lourdes Peña-Castillo
  • Marcus A. Moore
  • Dawn R. D. Bignell
  • Kapil Tahlan
Genetics and Molecular Biology of Industrial Organisms


The genus Streptomyces comprises bacteria that undergo a complex developmental life cycle and produce many metabolites of importance to industry and medicine. Streptomyces clavuligerus produces the β-lactamase inhibitor clavulanic acid, which is used in combination with β-lactam antibiotics to treat certain β-lactam resistant bacterial infections. Many aspects of how clavulanic acid production is globally regulated in S. clavuligerus still remains unknown. We conducted comparative proteomics analysis using the wild type strain of S. clavuligerus and two mutants (ΔbldA and ΔbldG), which are defective in global regulators and vary in their ability to produce clavulanic acid. Approximately 33.5 % of the predicted S. clavuligerus proteome was detected and 192 known or putative regulatory proteins showed statistically differential expression levels in pairwise comparisons. Interestingly, the expression of many proteins whose corresponding genes contain TTA codons (predicted to require the bldA tRNA for translation) was unaffected in the bldA mutant.


Proteomics iTRAQ Streptomyces clavuligerus Secondary metabolism Clavulanic acid Biosynthesis Regulation 



Anti–anti-sigma factor


Anti-sigma factor


Clavulanic acid


Conserved domain database


Database of domain-centric ontologies


False discovery rate


Fourier transformed


Higher-energy collisional dissociation


High performance liquid chromatography


Isobaric tags for relative and absolute quantitation


International Streptomyces project


Liquid chromatography


Maltose-yeast extract-malt extract


Methyl methanethiosulfonate


Tandem mass spectrometer/spectrometry


Starch asparagine


Streptomyces antibiotic regulatory protein


Sodium dodecyl sulfate


Tris(2-carboxyethyl)phosphine hydrochloride


Two component system


Triethylammonium bicarbonate


Trypticase soy broth with starch


Wild type



The described work was funded by start-up and operating grants from the Research and Development Corporation of Newfoundland and Labrador (RDC: 5404.1218.102) and the Natural Science and Engineering Research Council of Canada (NSERC: 386417-2010) to KT, respectively. Equipment used in the study was purchased with grants from the Canadian Foundation for Innovation (CFI), RDC and NSERC to KT and DRDB. NLF and MAM also received support from the Memorial University of Newfoundland to pursue their programs of study.

Supplementary material

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Copyright information

© Society for Industrial Microbiology and Biotechnology 2016

Authors and Affiliations

  • Nicole L. Ferguson
    • 1
  • Lourdes Peña-Castillo
    • 1
    • 2
  • Marcus A. Moore
    • 1
  • Dawn R. D. Bignell
    • 1
  • Kapil Tahlan
    • 1
  1. 1.Department of BiologyMemorial University of NewfoundlandSt. John’sCanada
  2. 2.Department of Computer ScienceMemorial University of NewfoundlandSt. John’sCanada

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