Home LiteratureArticle Details
PMID: 12730372 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The two-component PhoR-PhoP system controls both primary metabolism and secondary metabolite biosynthesis in Streptomyces lividans.

Sola-Landa A, Moura RS, Martín JF

Abstract

The biosynthesis of most secondary metabolites in different bacteria is strongly depressed by inorganic phosphate. The two-component phoR-phoP system of Streptomyces lividans has been cloned and characterized. PhoR showed all of the characteristics of the membrane-bound sensor proteins, whereas PhoP is a member of the DNA-binding OmpR family. Deletion mutants lacking phoP or phoR-phoP, were unable to grow in minimal medium at low phosphate concentration (10 microM). Growth was fully restored by complementation with the phoR-phoP genes. Both S. lividans DeltaphoP and DeltaphoR-phoP deletion mutants were unable to synthesize extracellular alkaline phosphatase (AP) as shown by immunodetection with anti-AP antibodies and by enzymatic analysis, suggesting that the PhoR-PhoP system is required for expression of the AP gene (phoA). Synthesis of AP was restored by complementation of the deletion mutants with phoR-phoP. The biosynthesis of two secondary metabolites, actinorhodin and undecylprodigiosin, was significantly increased in both solid and liquid medium in the DeltaphoP or DeltaphoR-phoP deletion mutants. Negative phosphate control of both secondary metabolites was restored by complementation with the phoR-phoP cluster. These results prove that expression of both phoA and genes implicated in the biosynthesis of secondary metabolites in S. lividans is regulated by a mechanism involving the two-component PhoR-PhoP system.

MeSH Terms
Amino Acid Sequence Bacterial Proteins/genetics,metabolism Genes, Bacterial Kinetics Molecular Sequence Data Phosphates/metabolism Plasmids Restriction Mapping Sequence Alignment Sequence Homology, Amino Acid Streptomyces/genetics,growth & development,metabolism
Chemicals
Bacterial Proteins PhoQ protein, Bacteria Phosphates PhoR protein, Bacteria
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sola-Landa A
Instituto de Biotecnologia de León (INBIOTEC), Parque Cientifico de León, Avenida del Real, n degrees 1, Spain.
Moura R S
Martín J F
References (27)
27 references, click to expand
  1. Molecular characterization of the mycobacterial SenX3-RegX3 two-component system: evidence for autoregulation.
    Microbiology. 2000 Dec;146 Pt 12:3091-8 PMID: 11101667
  2. Nutritional control of actinorhodin production by Streptomyces coelicolor A3(2): suppressive effects of nitrogen and phosphate.
    Appl Microbiol Biotechnol. 1990 Jan;32(4):449-54 PMID: 1366394
  3. Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways in Streptomyces coelicolor using DNA microarrays.
    Genes Dev. 2001 Dec 1;15(23):3183-92 PMID: 11731481
  4. The polyphosphate kinase plays a negative role in the control of antibiotic production in Streptomyces lividans.
    Mol Microbiol. 2002 Feb;43(4):919-30 PMID: 11929542
  5. Regulatory interactions between the Pho and sigma(B)-dependent general stress regulons of Bacillus subtilis.
    Microbiology. 2002 May;148(Pt 5):1593-602 PMID: 11988534
  6. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).
    Nature. 2002 May 9;417(6885):141-7 PMID: 12000953
  7. Specific inhibition of candicidin biosynthesis by the lipogenic inhibitor cerulenin.
    Biochim Biophys Acta. 1975 Dec 5;411(2):186-94 PMID: 811262
  8. Studies on transformation of Escherichia coli with plasmids.
    J Mol Biol. 1983 Jun 5;166(4):557-80 PMID: 6345791
  9. Production of nanaomycin and other antibiotics by phosphate-depressed fermentation using phosphate-trapping agents.
    J Antibiot (Tokyo). 1986 Nov;39(11):1557-64 PMID: 3793625
  10. Protein phosphorylation and regulation of adaptive responses in bacteria.
    Microbiol Rev. 1989 Dec;53(4):450-90 PMID: 2556636
  11. Signal transduction in the phosphate regulon of Escherichia coli involves phosphotransfer between PhoR and PhoB proteins.
    J Mol Biol. 1989 Dec 5;210(3):551-9 PMID: 2693738
  12. Phosphate control sequences involved in transcriptional regulation of antibiotic biosynthesis.
    Trends Biotechnol. 1990 Jul;8(7):184-9 PMID: 1366623
  13. Phosphate control of pabS gene transcription during candicidin biosynthesis.
    Gene. 1990 Sep 1;93(1):79-84 PMID: 1699847
  14. Communication modules in bacterial signaling proteins.
    Annu Rev Genet. 1992;26:71-112 PMID: 1482126
  15. Sequential action of two-component genetic switches regulates the PHO regulon in Bacillus subtilis.
    J Bacteriol. 1994 Mar;176(5):1348-58 PMID: 8113174
  16. Protein histidine kinases and signal transduction in prokaryotes and eukaryotes.
    Trends Genet. 1994 Apr;10(4):133-8 PMID: 8029829
  17. The signal-transduction network for Pho regulation in Bacillus subtilis.
    Mol Microbiol. 1996 Mar;19(5):933-9 PMID: 8830274
  18. A set of ordered cosmids and a detailed genetic and physical map for the 8 Mb Streptomyces coelicolor A3(2) chromosome.
    Mol Microbiol. 1996 Jul;21(1):77-96 PMID: 8843436
  19. Escherichia coli positive regulator OmpR has a large loop structure at the putative RNA polymerase interaction site.
    Nat Struct Biol. 1997 Jan;4(1):28-31 PMID: 8989318
  20. Structure of the DNA-binding domain of the OmpR family of response regulators.
    Mol Microbiol. 1997 May;24(3):665-7 PMID: 9179858
  21. Structural relationships in the OmpR family of winged-helix transcription factors.
    J Mol Biol. 1997 Jun 13;269(3):301-12 PMID: 9199401
  22. Bacillus subtilis PhoP binds to the phoB tandem promoter exclusively within the phosphate starvation-inducible promoter.
    J Bacteriol. 1997 Oct;179(20):6302-10 PMID: 9335276
  23. Actinorhodin and undecylprodigiosin production in wild-type and relA mutant strains of Streptomyces coelicolor A3(2) grown in continuous culture.
    FEMS Microbiol Lett. 1998 Nov 15;168(2):221-6 PMID: 9835032
  24. Phosphate control of oxytetracycline production by Streptomyces rimosus is at the level of transcription from promoters overlapped by tandem repeats similar to those of the DNA-binding sites of the OmpR family.
    J Bacteriol. 1999 May;181(10):3025-32 PMID: 10322002
  25. Sequential expression of macromolecule biosynthesis and candicidin formation in Streptomyces griseus.
    J Gen Microbiol. 1977 Oct;102(2):269-77 PMID: 411890
  26. Control of antibiotic biosynthesis.
    Microbiol Rev. 1980 Jun;44(2):230-51 PMID: 6991900
  27. Substrate analysis and molecular cloning of the extracellular alkaline phosphatase of Streptomyces griseus.
    Microbiology. 2001 Jun;147(Pt 6):1525-33 PMID: 11390683
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2003-05-13
Epub
2003-00-02
Pages
6133-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC156338
Subset
IM
Databases
GENBANK
AJ544582
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com