title: Proteomics analysis of global regulatory cascades involved in clavulanic acid production and morphological development in Streptomyces clavuligerus.
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.
authors.affiliation: Department of Biology, Memorial University of Newfoundland, St. John's, NL, A1B 3X9, Canada.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Ferguson
authors.affiliation: Department of Biology, Memorial University of Newfoundland, St. John's, NL, A1B 3X9, Canada.|Department of Computer Science, Memorial University of Newfoundland, St. John's, NL, A1B 3X5, Canada.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Peña-Castillo
authors.affiliation: Department of Biology, Memorial University of Newfoundland, St. John's, NL, A1B 3X9, Canada.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Moore
authors.affiliation: Department of Biology, Memorial University of Newfoundland, St. John's, NL, A1B 3X9, Canada.
authors.forename: Dawn R D
authors.initials: DR
authors.lastname: Bignell
authors.affiliation: Department of Biology, Memorial University of Newfoundland, St. John's, NL, A1B 3X9, Canada. ktahlan@mun.ca.
authors.forename: Kapil
authors.initials: K
authors.lastname: Tahlan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D019818:Clavulanic Acid / Q000096:biosynthesis*; D003062:Codon / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D013302:Streptomyces / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D065093:beta-Lactamase Inhibitors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003062:Codon; D020543:Proteome; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid
keywords: Biosynthesis; Clavulanic acid; Proteomics; Regulation; Secondary metabolism; Streptomyces clavuligerus; iTRAQ