Original Article

Self-control of the PHO regulon: the PhoP-dependent protein PhoU controls negatively expression of genes of PHO regulon in Streptomyces coelicolor

Published online:


Phosphate control of the biosynthesis of secondary metabolites in Streptomyces is mediated by the two component system PhoR–PhoP. Linked to the phoR–phoP cluster, and expressed in the opposite orientation, is a phoU-like encoding gene with low identity to the phoU gene of Escherichia coli. Expression of this phoU-like gene is strictly dependent on PhoP activation. We have isolated a PhoU-null mutant and used transcriptomic and RNA-sequencing (RNA-seq) procedures to identify its transcription start site and regulation. RNA-seq studies identified two transcription start sites, one upstream of phoU and the second upstream of the mptA gene. Whereas transcription of PhoU is entirely dependent on PhoP, expression of the downstream mtpA gene is only partially dependent on PhoP activation. The phoU mutant grows more slowly than the parental strain, sporulates poorly and the spores lack pigmentation. Production of actinorhodin and undecylprodigiosin decreased in the phoU mutant, indicating that PhoU has a positive modulating effect on production of these antibiotics. Indeed, transcriptional studies of expression of the actII-ORF4 and redD genes indicated that the PhoU protein activates expression of these antibiotic regulators. Using the glpQ1 promoter as in vivo reporter of the activity of the PHO regulon genes, we observed that expression of glpQ1 is negatively modulated by PhoU. These results were confirmed by reverse transcription-PCR studies of three genes of the PHO regulon; that is, glpQ1, pstS and phoR. In conclusion, PhoU acts as a negative modulator of expression of the PHO regulon genes and as phoU expression is strictly dependent on PhoP activation, this mechanism appears to work as a feed-back control mechanism (self-regulation).

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This article was supported by CICYT Grants BIO2010-16094 and ERA-IB PIM2010EEI-00677 of the Ministry of Economy and Competitivity, Madrid, Spain. Seomara Martín-Martín and Etelvina Franco received PhD fellowships from the Ministry of Science and Innovation (Madrid, Spain) and the Diputación de León (León), respectively.

Author information


  1. Instituto de Biotecnología de León (INBIOTEC), León, Spain

    • Seomara Martín-Martín
    • , Antonio Rodríguez-García
    • , Etelvina Franco-Domínguez
    •  & Alberto Sola-Landa
  2. Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne, UK

    • Fernando Santos-Beneit
  3. Área de Microbiología, Departamento de Biología Molecular, Facultad de Ciencias Biológicas y Ambientales, Universidad de León, Campus de Vegazana s/n, León, Spain

    • Juan Francisco Martín


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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to Juan Francisco Martín.