Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina.

Anna Maria Puglia, Fabio Sangiorgi, Rosa Alduina, Giuseppe Gallo, Jette Thykaer, Andrea Scaloni, Giovanni Renzone, Tilmann Weber, Anna Eliasson Lantz, Efthimia Stegmann

Risultato della ricerca: Article

20 Citazioni (Scopus)

Abstract

A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially and constitutively expressed protein isoforms, which were associated to 203 ORFs in the A. balhimycina genome. These data, providing insights on the major metabolic pathways/molecular processes operating in this organism, were used to compile 2-DE reference maps covering 3-10, 4-7 and 4.5-5.5 pH gradients available over the World Wide Web as interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps). Functional clustering analysis revealed that differentially expressed proteins belong to functional groups involved in central carbon metabolism, amino acid metabolism and protein biosynthesis, energetic and redox balance, sugar/amino sugar metabolism, balhimycin biosynthesis and transcriptional regulation or with hypothetical and/or unknown function. Interestingly, proteins involved in the biosynthesis of balhymycin precursors, such as amino acids, amino sugars and central carbon metabolism intermediates, were up-regulated during antibiotic production. qRT-PCR analysis revealed that 8 out of 14 up-regulated genes showed a positive correlation between changes at translational and transcriptional expression level. Furthermore, proteomic analysis of two non-producing mutants, restricted to a sub-set of differentially expressed proteins, showed that most proteins required for the biosynthesis of balhimycin precursors are down-regulated in both mutants. These findings suggest that primary metabolic pathways support anabolic routes leading to balhimycin biosynthesis and the differentially expressed genes are interesting targets for the construction of high-yielding producer strains by rational genetic engineering.
Lingua originaleEnglish
pagine (da-a)-
Numero di pagine20
RivistaProteomics
Volume2010-01
Stato di pubblicazionePublished - 2010

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Biosynthesis
Metabolism
Proteomics
Anti-Bacterial Agents
Amino Sugars
Genes
Protein Biosynthesis
Metabolic Networks and Pathways
Proteins
Carbon
Amino Acids
Genetic engineering
Proton-Motive Force
Genetic Engineering
Actinobacteria
Proteome
Vancomycin
Sugars
World Wide Web
Internet

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry

Cita questo

Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina. / Puglia, Anna Maria; Sangiorgi, Fabio; Alduina, Rosa; Gallo, Giuseppe; Thykaer, Jette; Scaloni, Andrea; Renzone, Giovanni; Weber, Tilmann; Lantz, Anna Eliasson; Stegmann, Efthimia.

In: Proteomics, Vol. 2010-01, 2010, pag. -.

Risultato della ricerca: Article

Puglia, Anna Maria ; Sangiorgi, Fabio ; Alduina, Rosa ; Gallo, Giuseppe ; Thykaer, Jette ; Scaloni, Andrea ; Renzone, Giovanni ; Weber, Tilmann ; Lantz, Anna Eliasson ; Stegmann, Efthimia. / Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina. In: Proteomics. 2010 ; Vol. 2010-01. pagg. -.
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title = "Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina.",
abstract = "A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially and constitutively expressed protein isoforms, which were associated to 203 ORFs in the A. balhimycina genome. These data, providing insights on the major metabolic pathways/molecular processes operating in this organism, were used to compile 2-DE reference maps covering 3-10, 4-7 and 4.5-5.5 pH gradients available over the World Wide Web as interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps). Functional clustering analysis revealed that differentially expressed proteins belong to functional groups involved in central carbon metabolism, amino acid metabolism and protein biosynthesis, energetic and redox balance, sugar/amino sugar metabolism, balhimycin biosynthesis and transcriptional regulation or with hypothetical and/or unknown function. Interestingly, proteins involved in the biosynthesis of balhymycin precursors, such as amino acids, amino sugars and central carbon metabolism intermediates, were up-regulated during antibiotic production. qRT-PCR analysis revealed that 8 out of 14 up-regulated genes showed a positive correlation between changes at translational and transcriptional expression level. Furthermore, proteomic analysis of two non-producing mutants, restricted to a sub-set of differentially expressed proteins, showed that most proteins required for the biosynthesis of balhimycin precursors are down-regulated in both mutants. These findings suggest that primary metabolic pathways support anabolic routes leading to balhimycin biosynthesis and the differentially expressed genes are interesting targets for the construction of high-yielding producer strains by rational genetic engineering.",
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AU - Puglia, Anna Maria

AU - Sangiorgi, Fabio

AU - Alduina, Rosa

AU - Gallo, Giuseppe

AU - Thykaer, Jette

AU - Scaloni, Andrea

AU - Renzone, Giovanni

AU - Weber, Tilmann

AU - Lantz, Anna Eliasson

AU - Stegmann, Efthimia

PY - 2010

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N2 - A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially and constitutively expressed protein isoforms, which were associated to 203 ORFs in the A. balhimycina genome. These data, providing insights on the major metabolic pathways/molecular processes operating in this organism, were used to compile 2-DE reference maps covering 3-10, 4-7 and 4.5-5.5 pH gradients available over the World Wide Web as interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps). Functional clustering analysis revealed that differentially expressed proteins belong to functional groups involved in central carbon metabolism, amino acid metabolism and protein biosynthesis, energetic and redox balance, sugar/amino sugar metabolism, balhimycin biosynthesis and transcriptional regulation or with hypothetical and/or unknown function. Interestingly, proteins involved in the biosynthesis of balhymycin precursors, such as amino acids, amino sugars and central carbon metabolism intermediates, were up-regulated during antibiotic production. qRT-PCR analysis revealed that 8 out of 14 up-regulated genes showed a positive correlation between changes at translational and transcriptional expression level. Furthermore, proteomic analysis of two non-producing mutants, restricted to a sub-set of differentially expressed proteins, showed that most proteins required for the biosynthesis of balhimycin precursors are down-regulated in both mutants. These findings suggest that primary metabolic pathways support anabolic routes leading to balhimycin biosynthesis and the differentially expressed genes are interesting targets for the construction of high-yielding producer strains by rational genetic engineering.

AB - A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially and constitutively expressed protein isoforms, which were associated to 203 ORFs in the A. balhimycina genome. These data, providing insights on the major metabolic pathways/molecular processes operating in this organism, were used to compile 2-DE reference maps covering 3-10, 4-7 and 4.5-5.5 pH gradients available over the World Wide Web as interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps). Functional clustering analysis revealed that differentially expressed proteins belong to functional groups involved in central carbon metabolism, amino acid metabolism and protein biosynthesis, energetic and redox balance, sugar/amino sugar metabolism, balhimycin biosynthesis and transcriptional regulation or with hypothetical and/or unknown function. Interestingly, proteins involved in the biosynthesis of balhymycin precursors, such as amino acids, amino sugars and central carbon metabolism intermediates, were up-regulated during antibiotic production. qRT-PCR analysis revealed that 8 out of 14 up-regulated genes showed a positive correlation between changes at translational and transcriptional expression level. Furthermore, proteomic analysis of two non-producing mutants, restricted to a sub-set of differentially expressed proteins, showed that most proteins required for the biosynthesis of balhimycin precursors are down-regulated in both mutants. These findings suggest that primary metabolic pathways support anabolic routes leading to balhimycin biosynthesis and the differentially expressed genes are interesting targets for the construction of high-yielding producer strains by rational genetic engineering.

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