A novel family of proteins that regulates antibiotic production in streptomycetes appears to contain an OmpR‐like DNA‐binding fold

Wietzorrek, Andreas; Bibb, Mervyn J.

doi:10.1046/j.1365-2958.1997.5421903.x

Cited by 285 publications

(274 citation statements)

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“…2). The N-terminal portion of AfsR has already been shown to be related to a family of proteins involved in activating some antibiotic synthesis clusters (the SARP family ; Wietzorrek & Bibb, 1997) ; however, it had not been previously recognized that the remainder of the AfsR sequence is related to the MalT family of activators, although it is of a similar size and the presence of a DNA-binding domain at the same C-terminal position had already been recognized (Horinouchi et al, 1990). Therefore, AfsR appears to be a hybrid regulator, related to the SARP family of activators at its N-terminus and to the MalT family at its C-terminus ; this explains why both ends of the protein can function independently in activating antibiotic production (Horinouchi et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, these protein sequences appear to define a novel family of bacterial regulatory proteins. Of particular interest is the inclusion from the - search of the AfsR protein as a member of this family, because the N-terminal portion of AfsR has demonstrated homology to the family of Streptomyces antibiotic regulatory proteins (SARPs ; Wietzorrek & Bibb, 1997). A tree was constructed by the neighbour-joining method to reveal relationships between the different members of this protein family, which we call the MalT family of bacterial regulators (Fig.…”

Section: Lipr Homologues Are Members Of a Novel Family Of Bacterial Rmentioning

confidence: 99%

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The Streptomyces coelicolor A3(2) lipAR operon encodes an extracellular lipase and a new type of transcriptional regulator The GenBank accession numbers for the sequences described in this paper are AF009336 and U03114.

et al. 1999

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Section: Discussionmentioning

confidence: 99%

Section: Lipr Homologues Are Members Of a Novel Family Of Bacterial Rmentioning

confidence: 99%

The Streptomyces coelicolor A3(2) lipAR operon encodes an extracellular lipase and a new type of transcriptional regulator The GenBank accession numbers for the sequences described in this paper are AF009336 and U03114.

et al. 1999

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“…Two putative regulatory genes have been identified in the mithramycin gene cluster: mtmR, which encodes a SARPtype activator protein (Wietzorrek & Bibb, 1997) that was previously proposed to be an activator of mithramycin biosynthesis (Lombó et al, 1999), and mtrY, which is 40 kb away from mtmR and codes for a putative regulatory protein (Garcia-Bernardo et al, 2000). Comparisons of MtrY with proteins in databases showed similarities with several PadR-like proteins of unknown function from different actinomycetes, such as GenBank accession number AFO53534 from Streptomyces sp.…”

Section: Role Of Mtmr and Mtry In Mithramycin Productionmentioning

confidence: 99%

Transcriptional regulation of mithramycin biosynthesis in Streptomyces argillaceus: dual role as activator and repressor of the PadR-like regulator MtrY

et al. 2015

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The mithramycin biosynthesis gene cluster of Streptomyces argillaceus ATCC 12956 contains 34 ORFs and includes two putative regulatory genes (mtmR and mtrY), which encode proteins of the SARP (Streptomyces antibiotic regulatory protein) and PadR transcriptional regulator families, respectively. MtmR was proposed to behave as a positive regulator of mithramycin biosynthesis. Inactivation and overexpression of mtrY indicated that it is also a positive regulator of mithramycin biosynthesis, being non-essential but required to maintain high levels of mithramycin production in the producer strain. Transcriptional analyses by reverse transcription PCR and quantitative realtime PCR of mithramycin genes, and promoter-probe assays in S. argillaceus polyketide synthase and regulatory mutants and the WT strain, and in the heterologous host Streptomyces albus, were carried out to analyse the role of MtmR and MtrY in the regulation of the mithramycin gene cluster. These experiments revealed that MtmR had a positive role, activating expression of at least six polycistronic units (mtmR-mtmE, mtmQ-mtmTII, mtmX-mtmY, mtmV-mtmTIII, mtmW-mtmMI and mtmGI-mtrB) and one monocistronic unit (mtmGII) in the mithramycin gene cluster. However, MtrY played a dual role in the mithramycin gene cluster: (i) repressing the expression of resistance genes and its coding gene itself by controlling the activity of the mtrYp promoter that directs expression of the regulator mtrY and resistance genes, with this repression being released in the presence of mithramycin; and (ii) enhancing the expression of mithramycin biosynthesis genes when mithramycin is present, by interacting with the mtmRp promoter that controls expression of the mtmR regulator, amongst others.

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“…The ACT biosynthetic gene cluster consists of five transcription units and actII-ORF4 encodes the key activator of ACT production (Wietzorrek & Bibb, 1997). A complex network has been revealed to regulate the biosynthesis of ACT, involving small molecules (ppGpp, N-acetylglucosamine and c-butyrolactone), two-component systems, RNA regulation and so on van Wezel & McDowall, 2011).…”

Section: Introductionmentioning

confidence: 99%

GntR family regulator SCO6256 is involved in antibiotic production and conditionally regulates the transcription of myo-inositol catabolic genes in Streptomyces coelicolor A3(2)

Gao

et al. 2016

Microbiology

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SCO6256 belongs to the GntR family and shows 74 % identity with SCO6974, which is the repressor of myo-inositol catabolism in Streptomyces coelicolor A3(2). Disruption of SCO6256 significantly enhanced the transcription of myo-inositol catabolic genes in R2YE medium. The purified recombinant SCO6256 directly bound to the upstream regions of SCO2727, SCO6978 and SCO6985, as well as its encoding gene. Footprinting assays demonstrated that SCO6256 bound to the same sites in the myo-inositol catabolic gene cluster as SCO6974. The expression of SCO6256 was repressed by SCO6974 in minimal medium with myo-inositol as the carbon source, but not in R2YE medium. Glutathione-S-transferase pull-down assays demonstrated that SCO6974 and SCO6256 interacted with each other; and both of the proteins controlled the transcription of myo-inositol catabolic genes in R2YE medium. These results indicated SCO6256 regulates the transcription of myo-inositol catabolic genes in coordination with SCO6974 in R2YE medium. In addition, SCO6256 negatively regulated the production of actinorhodin and calcium-dependent antibiotic via control of the transcription of actII-ORF4 and cdaR. SCO6256 bound to the upstream region of cdaR and the binding sequence was proved to be TTTCGGCACGCAGACAT, which was further confirmed through base substitution. Four putative targets (SCO2652, SCO4034, SCO4237 and SCO6377) of SCO6256 were found by screening the genome sequence of Strep. coelicolor A3(2) based on the conserved binding motif, and confirmed by transcriptional analysis and electrophoretic mobility shift assays. These results revealed that SCO6256 is involved in the regulation of myo-inositol catabolic gene transcription and antibiotic production in Strep. coelicolor A3(2).

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A novel family of proteins that regulates antibiotic production in streptomycetes appears to contain an OmpR‐like DNA‐binding fold

Cited by 285 publications

References 0 publications

The Streptomyces coelicolor A3(2) lipAR operon encodes an extracellular lipase and a new type of transcriptional regulator The GenBank accession numbers for the sequences described in this paper are AF009336 and U03114.

The Streptomyces coelicolor A3(2) lipAR operon encodes an extracellular lipase and a new type of transcriptional regulator The GenBank accession numbers for the sequences described in this paper are AF009336 and U03114.

Transcriptional regulation of mithramycin biosynthesis in Streptomyces argillaceus: dual role as activator and repressor of the PadR-like regulator MtrY

GntR family regulator SCO6256 is involved in antibiotic production and conditionally regulates the transcription of myo-inositol catabolic genes in Streptomyces coelicolor A3(2)

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