Dataset Information

Identification of PimR as a positive regulator of pimaricin biosynthesis in Streptomyces natalensis.

ABSTRACT: Sequencing of the DNA region on the left fringe of the pimaricin gene cluster revealed the presence of a 3.6-kb gene, pimR, whose deduced product (1,198 amino acid residues) was found to have amino acid sequence homology with bacterial regulatory proteins. Database comparisons revealed that PimR represents the archetype of a new class of regulators, combining a Streptomyces antibiotic regulatory protein (SARP)-like N-terminal section with a C-terminal half homologous to guanylate cyclases and large ATP-binding regulators of the LuxR family. Gene replacement of pimR from Streptomyces natalensis chromosome results in a complete loss of pimaricin production, suggesting that PimR is a positive regulator of pimaricin biosynthesis. Gene expression analysis by reverse transcriptase PCR (RT-PCR) of the pimaricin gene cluster revealed that S. natalensis DeltaPimR shows no expression at all of the cholesterol oxidase-encoding gene pimE, and very low level transcription of the remaining genes of the cluster except for the mutant pimR gene, thus demonstrating that this regulator activates the transcription of all the genes belonging to the pimaricin gene cluster but not its own transcription.

SUBMITTER: Anton N

PROVIDER: S-EPMC387814 | biostudies-literature | 2004 May

REPOSITORIES: biostudies-literature

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Identification of PimR as a positive regulator of pimaricin biosynthesis in Streptomyces natalensis.

Antón Nuria N Mendes Marta V MV Martín Juan F JF Aparicio Jesús F JF

Journal of bacteriology 20040501 9

Sequencing of the DNA region on the left fringe of the pimaricin gene cluster revealed the presence of a 3.6-kb gene, pimR, whose deduced product (1,198 amino acid residues) was found to have amino acid sequence homology with bacterial regulatory proteins. Database comparisons revealed that PimR represents the archetype of a new class of regulators, combining a Streptomyces antibiotic regulatory protein (SARP)-like N-terminal section with a C-terminal half homologous to guanylate cyclases and la ...[more]

PMID: 15090496

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Project description:BACKGROUND: Polyenes represent a major class of antifungal agents characterised by the presence of a series of conjugated double bonds in their planar hydroxylated macrolide ring structure. Despite their general interest, very little is known about the factors that modulate their biosynthesis. Among these factors, we have recently discovered a new inducing compound (PI-factor) in the pimaricin producer Streptomyces natalensis, which elicits polyene production in a manner characteristic of quorum sensing. Here, we describe the involvement of an amino-acid exporter from S. natalensis in modulating the expression of pimaricin biosynthetic genes via secretion of the quorum-sensing pimaricin-inducer PI-factor. RESULTS: Adjacent to the pimaricin gene cluster lies a member of the RhtB family of amino-acid exporters. Gene deletion and complementation experiments provided evidence for a role for PimT in the export of L-homoserine, L-serine, and L-homoserine lactone. Expression of the gene was shown to be induced by homoserine and by the quorum-sensing pimaricin-inducer PI-factor. Interestingly, the mutant displayed 65% loss of pimaricin production, and also 50% decrease in the production of PI, indicating that PimT is used as PI-factor exporter, and suggesting that the effect in antifungal production might be due to limited secretion of the inducer. CONCLUSION: This report describes the involvement of an amino acid exporter (encoded by pimT in the vicinity of the pimaricin cluster) in modulating the expression of antibiotic biosynthetic genes via secretion of the quorum-sensing pimaricin-inducer PI-factor. The discovery of the participation of amino acid exporters in a signal transduction cascade for the production of polyene macrolides is unexpected, and represents an important step forward towards understanding the regulatory network for polyene regulation. Additionally, this finding constitutes the first detailed characterization of an amino-acid exporter in an Actinomycete, and to our knowledge, the first evidence for the implication of this type of exporters in quorum sensing.

Dataset Information

Identification of PimR as a positive regulator of pimaricin biosynthesis in Streptomyces natalensis.

Publications

Identification of PimR as a positive regulator of pimaricin biosynthesis in Streptomyces natalensis.

Similar Datasets

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