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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

Abstract

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.

Keywords

Proteomics iTRAQ Streptomyces clavuligerus Secondary metabolism Clavulanic acid Biosynthesis Regulation 

Abbreviations

AASF

Anti–anti-sigma factor

ASF

Anti-sigma factor

CA

Clavulanic acid

CDD

Conserved domain database

dcGO

Database of domain-centric ontologies

FDR

False discovery rate

FT

Fourier transformed

HCD

Higher-energy collisional dissociation

HPLC

High performance liquid chromatography

iTRAQ

Isobaric tags for relative and absolute quantitation

ISP

International Streptomyces project

LC

Liquid chromatography

MYM

Maltose-yeast extract-malt extract

MMTS

Methyl methanethiosulfonate

MS/MS

Tandem mass spectrometer/spectrometry

SA

Starch asparagine

SARP

Streptomyces antibiotic regulatory protein

SDS

Sodium dodecyl sulfate

TCEP

Tris(2-carboxyethyl)phosphine hydrochloride

TCS

Two component system

TEAB

Triethylammonium bicarbonate

TSBS

Trypticase soy broth with starch

wt

Wild type

Notes

Acknowledgments

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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