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

  • Genetics and Molecular Biology of Industrial Organisms
  • Published:
Journal of Industrial Microbiology & Biotechnology

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.

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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

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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.

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  1. Department of Biology, Memorial University of Newfoundland, St. John’s, NL, A1B 3X9, Canada

    Nicole L. Ferguson, Lourdes Peña-Castillo, Marcus A. Moore, Dawn R. D. Bignell & Kapil Tahlan

  2. Department of Computer Science, Memorial University of Newfoundland, St. John’s, NL, A1B 3X5, Canada

    Lourdes Peña-Castillo

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  1. Nicole L. Ferguson
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Correspondence to Kapil Tahlan.

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Ferguson, N.L., Peña-Castillo, L., Moore, M.A. et al. Proteomics analysis of global regulatory cascades involved in clavulanic acid production and morphological development in Streptomyces clavuligerus . J Ind Microbiol Biotechnol 43, 537–555 (2016). https://doi.org/10.1007/s10295-016-1733-y

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