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PMID: 22194457 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Functional analysis of the N-acetylglucosamine metabolic genes of Streptomyces coelicolor and role in control of development and antibiotic production.

Journal of bacteriology ·Vol. 194 ·No. 5 ·2012-03-00 ·Pages 1136-44

Świątek MA, Tenconi E, Rigali S, van Wezel GP

Abstract

N-acetylglucosamine, the monomer of chitin, is a favored carbon and nitrogen source for streptomycetes. Its intracellular catabolism requires the combined actions of the N-acetylglucosamine-6-phosphate (GlcNAc-6P) deacetylase NagA and the glucosamine-6-phosphate (GlcN-6P) deaminase/isomerase NagB. GlcNAc acts as a signaling molecule in the DasR-mediated nutrient sensing system, activating development and antibiotic production under poor growth conditions (famine) and blocking these processes under rich conditions (feast). In order to understand how a single nutrient can deliver opposite information according to the nutritional context, we carried out a mutational analysis of the nag metabolic genes nagA, nagB, and nagK. Here we show that the nag genes are part of the DasR regulon in Streptomyces coelicolor, which explains their transcriptional induction by GlcNAc. Most likely as the result of the intracellular accumulation of GlcN-6P, nagB deletion mutants fail to grow in the presence of GlcNAc. This toxicity can be alleviated by the additional deletion of nagA. We recently showed that in S. coelicolor, GlcNAc is internalized as GlcNAc-6P via the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS). Considering the relevance of GlcNAc for the control of antibiotic production, improved insight into GlcNAc metabolism in Streptomyces may provide new leads toward biotechnological applications.

MeSH Terms
Acetylglucosamine/metabolism Anti-Bacterial Agents/biosynthesis Bacterial Proteins/genetics,metabolism DNA Mutational Analysis Gene Deletion Gene Expression Regulation, Bacterial Metabolic Networks and Pathways/genetics Regulon Streptomyces coelicolor/genetics,metabolism
Chemicals
Anti-Bacterial Agents Bacterial Proteins Acetylglucosamine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Świątek Magdalena A
Molecular Biotechnology, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
Tenconi Elodie
Rigali Sébastien
van Wezel Gilles P
References (47)
47 references, click to expand
  1. The dasABC gene cluster, adjacent to dasR, encodes a novel ABC transporter for the uptake of N,N'-diacetylchitobiose in Streptomyces coelicolor A3(2).
    Appl Environ Microbiol. 2007 May;73(9):3000-8 PMID: 17351098
  2. Unlocking Streptomyces spp. for use as sustainable industrial production platforms by morphological engineering.
    Appl Environ Microbiol. 2006 Aug;72(8):5283-8 PMID: 16885277
  3. Feast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces.
    EMBO Rep. 2008 Jul;9(7):670-5 PMID: 18511939
  4. Functional expression of the Cre recombinase in actinomycetes.
    Appl Microbiol Biotechnol. 2008 Apr;78(6):1065-70 PMID: 18299828
  5. Amino sugar sensitivity in Escherichia coli mutants unable to grow on N-acetylglucosamine.
    J Bacteriol. 1970 Feb;101(2):384-91 PMID: 4905307
  6. Evolutionary relationships between sugar kinases and transcriptional repressors in bacteria.
    Microbiology (Reading). 1994 Sep;140 ( Pt 9):2349-54 PMID: 7952186
  7. N-acetylglucosamine 6-phosphate deacetylase (nagA) is required for N-acetyl glucosamine assimilation in Gluconacetobacter xylinus.
    PLoS One. 2011;6(6):e18099 PMID: 21655093
  8. Reaction mechanism of phosphoglucosamine mutase from Escherichia coli.
    Eur J Biochem. 1999 May;262(1):202-10 PMID: 10231382
  9. ATP-binding cassette transport system involved in regulation of morphological differentiation in response to glucose in Streptomyces griseus.
    J Bacteriol. 2002 Jan;184(1):91-103 PMID: 11741848
  10. Convergent pathways for utilization of the amino sugars N-acetylglucosamine, N-acetylmannosamine, and N-acetylneuraminic acid by Escherichia coli.
    J Bacteriol. 1999 Jan;181(1):47-54 PMID: 9864311
  11. Recognition and degradation of chitin by streptomycetes.
    Antonie Van Leeuwenhoek. 2001 Sep;79(3-4):285-9 PMID: 11816971
  12. The regulation of the secondary metabolism of Streptomyces: new links and experimental advances.
    Nat Prod Rep. 2011 Jul;28(7):1311-33 PMID: 21611665
  13. Conserved cis-acting elements upstream of genes composing the chitinolytic system of streptomycetes are DasR-responsive elements.
    J Mol Microbiol Biotechnol. 2007;12(1-2):60-6 PMID: 17183212
  14. Apical hyphal extension in Streptomyces coelicolor A3(2).
    J Gen Microbiol. 1990 Jun;136(6):1077-84 PMID: 1696612
  15. Analysis of the nag regulon from Escherichia coli K12 and Klebsiella pneumoniae and of its regulation.
    Mol Gen Genet. 1989 Oct;219(1-2):97-105 PMID: 2693951
  16. Expression of Cre recombinase during transient phage infection permits efficient marker removal in Streptomyces.
    Nucleic Acids Res. 2006 Feb 09;34(3):e20 PMID: 16473843
  17. Autophosphorylation of phosphoglucosamine mutase from Escherichia coli.
    J Bacteriol. 2000 Mar;182(5):1280-5 PMID: 10671448
  18. The chitobiose-binding protein, DasA, acts as a link between chitin utilization and morphogenesis in Streptomyces coelicolor.
    Microbiology (Reading). 2008 Feb;154(Pt 2):373-382 PMID: 18227241
  19. The novel Streptomyces olivaceoviridis ABC transporter Ngc mediates uptake of N-acetylglucosamine and N,N'-diacetylchitobiose.
    Mol Genet Genomics. 2002 Jun;267(4):429-39 PMID: 12111550
  20. Streptomyces morphogenetics: dissecting differentiation in a filamentous bacterium.
    Nat Rev Microbiol. 2009 Jan;7(1):36-49 PMID: 19079351
  21. Control of amino sugar metabolism in Escherichia coli and isolation of mutants unable to degrade amino sugars.
    Biochem J. 1968 Feb;106(4):847-58 PMID: 4866432
  22. Repression and induction of the nag regulon of Escherichia coli K-12: the roles of nagC and nagA in maintenance of the uninduced state.
    Mol Microbiol. 1991 Aug;5(8):2053-62 PMID: 1766379
  23. Regulation of secondary metabolism in streptomycetes.
    Curr Opin Microbiol. 2005 Apr;8(2):208-15 PMID: 15802254
  24. Chapter 5. Applying the genetics of secondary metabolism in model actinomycetes to the discovery of new antibiotics.
    Methods Enzymol. 2009;458:117-41 PMID: 19374981
  25. The phosphotransferase system of Streptomyces coelicolor is biased for N-acetylglucosamine metabolism.
    J Bacteriol. 2003 Dec;185(23):7019-23 PMID: 14617669
  26. The permease gene nagE2 is the key to N-acetylglucosamine sensing and utilization in Streptomyces coelicolor and is subject to multi-level control.
    Mol Microbiol. 2010 Mar;75(5):1133-44 PMID: 20487300
  27. PREDetector: a new tool to identify regulatory elements in bacterial genomes.
    Biochem Biophys Res Commun. 2007 Jun 15;357(4):861-4 PMID: 17451648
  28. Cloning of genes governing the deoxysugar portion of the erythromycin biosynthesis pathway in Saccharopolyspora erythraea (Streptomyces erythreus).
    J Bacteriol. 1989 Nov;171(11):5872-81 PMID: 2681144
  29. The minimal replicon of a streptomycete plasmid produces an ultrahigh level of plasmid DNA.
    Plasmid. 1986 May;15(3):199-209 PMID: 3012613
  30. Carbon catabolite repression in bacteria: choice of the carbon source and autoregulatory limitation of sugar utilization.
    FEMS Microbiol Lett. 2002 Apr 9;209(2):141-8 PMID: 12007797
  31. Cloning, characterization and expression of beta-N-acetylglucosaminidase gene from Streptomyces thermoviolaceus OPC-520(1).
    Biochim Biophys Acta. 1998 Oct 23;1425(2):437-40 PMID: 9795260
  32. An alternative route for recycling of N-acetylglucosamine from peptidoglycan involves the N-acetylglucosamine phosphotransferase system in Escherichia coli.
    J Bacteriol. 2009 Sep;191(18):5641-7 PMID: 19617367
  33. The sugar phosphotransferase system of Streptomyces coelicolor is regulated by the GntR-family regulator DasR and links N-acetylglucosamine metabolism to the control of development.
    Mol Microbiol. 2006 Sep;61(5):1237-51 PMID: 16925557
  34. Structural and functional characterization of Streptomyces plicatus beta-N-acetylhexosaminidase by comparative molecular modeling and site-directed mutagenesis.
    J Biol Chem. 1998 Jul 31;273(31):19618-24 PMID: 9677388
  35. GlcP constitutes the major glucose uptake system of Streptomyces coelicolor A3(2).
    Mol Microbiol. 2005 Jan;55(2):624-36 PMID: 15659175
  36. The gate controlling cell wall synthesis in Staphylococcus aureus.
    Mol Microbiol. 2004 Aug;53(4):1221-31 PMID: 15306023
  37. The femR315 gene from Staphylococcus aureus, the interruption of which results in reduced methicillin resistance, encodes a phosphoglucosamine mutase.
    J Bacteriol. 1997 Sep;179(17):5321-5 PMID: 9286983
  38. Extending the classification of bacterial transcription factors beyond the helix-turn-helix motif as an alternative approach to discover new cis/trans relationships.
    Nucleic Acids Res. 2004 Jun 24;32(11):3418-26 PMID: 15247334
  39. Streptomyces olivaceoviridis possesses a phosphotransferase system that mediates specific, phosphoenolpyruvate-dependent uptake of N-acetylglucosamine.
    Mol Genet Genomics. 2002 Nov;268(3):344-51 PMID: 12436256
  40. The molecular biology of chitin digestion.
    Curr Opin Biotechnol. 1998 Jun;9(3):270-7 PMID: 9650272
  41. Copurification of glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase activities of Escherichia coli: characterization of the glmU gene product as a bifunctional enzyme catalyzing two subsequent steps in the pathway for UDP-N-acetylglucosamine synthesis.
    J Bacteriol. 1994 Sep;176(18):5788-95 PMID: 8083170
  42. High expression levels of chitinase genes in Streptomyces coelicolor A3(2) grown in soil.
    FEMS Microbiol Ecol. 2011 Sep;77(3):623-35 PMID: 21631548
  43. Glucose kinase of Streptomyces coelicolor A3(2): large-scale purification and biochemical analysis.
    Antonie Van Leeuwenhoek. 2000 Dec;78(3-4):253-61 PMID: 11386347
  44. Growth polarity and cell division in Streptomyces.
    Curr Opin Microbiol. 2003 Dec;6(6):564-71 PMID: 14662351
  45. Lack of A-factor production induces the expression of nutrient scavenging and stress-related proteins in Streptomyces griseus.
    Mol Cell Proteomics. 2009 Oct;8(10):2396-403 PMID: 19625340
  46. Purification, molecular and kinetic properties of glucosamine-6-phosphate isomerase (deaminase) from Escherichia coli.
    Biochim Biophys Acta. 1984 Jun 14;787(2):165-73 PMID: 6375729
  47. Why does Escherichia coli grow more slowly on glucosamine than on N-acetylglucosamine? Effects of enzyme levels and allosteric activation of GlcN6P deaminase (NagB) on growth rates.
    J Bacteriol. 2005 May;187(9):2974-82 PMID: 15838023
Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
1098-5530
Published
2012-03-00
Epub
2011-00-22
Pages
1136-44
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC3294797
Subset
IM
Corrections
CommentIn
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