Identification of PimR as a Positive Regulator of Pimaricin Biosynthesis in
            <i>Streptomyces natalensis</i>

Antón, Nuria; Mendes, Marta V.; Martı́n, Juan F.; Aparicio, Jesús F.

doi:10.1128/jb.186.9.2567-2575.2004

Cited by 92 publications

(75 citation statements)

References 41 publications

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“…The transcription of scnK in both mutants was reduced, and very low level transcription of scnJ was observed in the DscnRI mutant strain. Interestingly, this transcription pattern was quite different from that of earlier studies of the pim cluster (Antó n et al, 2004(Antó n et al, , 2007, in which pimE was hardly affected in a DpimM (scnRII orthologue) mutant, and the transcription of most genes still remained detectable in DpimR (scnRI orthologue) and DpimM mutants.…”

Section: Resultscontrasting

confidence: 51%

“…An earlier study (Antó n et al, 2004) and our unpublished data reveal that all genes of the NTM biosynthetic gene cluster are dramatically decreased in expression in the scnRI (pimR) disrupted mutant, and that these mutants are defective in NTM production. The trace expression level of scnRI observed in the DadpA ch mutant may not be sufficient to activate the NTM cluster, resulting in an NTM-nonproducing phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…The biosynthetic gene cluster for NTM in Streptomyces natalensis has been cloned (Aparicio et al, 2000) and shown to contain 19 ORFs spanning a distance of 88.6 kb (Vicente et al, 2009), including two pathway-specific positive regulator genes, pimR and pimM. Both DpimR and DpimM mutants are defective in NTM production (Antó n et al, 2004(Antó n et al, , 2007. Several other NTM biosynthesis-related regulators located outside the biosynthetic gene cluster have also been identified in S. natalensis, including the twocomponent PhoP-PhoR system (Mendes et al, 2007) and the butyrolactone regulon (Lee et al, 2005(Lee et al, , 2008).…”

Section: Introductionmentioning

confidence: 99%

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The pleitropic regulator AdpAch is required for natamycin biosynthesis and morphological differentiation in Streptomyces chattanoogensis

Zhou

et al. 2011

Microbiology

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The complete natamycin (NTM) biosynthetic gene cluster of Streptomyces chattanoogensis was cloned and confirmed by the disruption of pathway-specific activator genes. Comparative cluster analysis with its counterpart in Streptomyces natalensis revealed different cluster architecture between these two clusters. Compared with the highly conserved coding sequences, sequence variations appear to occur frequently in the intergenic regions. The evolutionary change of nucleotide sequence in the intergenic regions has given rise to different transcriptional organizations in the two clusters and resulted in altered gene regulation. These results provide insight into the evolution of antibiotic biosynthetic gene clusters. In addition, we cloned a pleitropic regulator gene, adpA ch , in S. chattanoogensis. Using the genetic system that we developed for this strain, adpA ch was deleted from the genome of S. chattanoogensis. The DadpA ch mutant showed a conditionally sparse aerial mycelium formation phenotype and defects in sporulation; it also lost the ability to produce NTM and a diffusible yellow pigment normally produced by S. chattanoogensis. RT-PCR analysis revealed that transcription of adpA ch was constitutive in YEME liquid medium. By using rapid amplification of 59 complementary DNA ends, two transcription start sites were identified upstream of the adpA ch coding region. Quantitative transcriptional analysis showed that the expression level of the NTM regulatory gene scnRI decreased 20-fold in the DadpA ch mutant strain, while the transcription of the other activator gene scnRII was not significantly affected. Electrophoretic mobility shift assay (EMSA) showed that AdpA ch binds to its own promoter but fails to bind to the promoter region of scnRI, indicating that the control of scnRI by AdpA ch is exerted in an indirect way. This work not only provides a platform and a new potential target for increasing the titre of NTM by genetic manipulation, but also advances the understanding of the regulation of NTM biosynthesis.

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Section: Resultscontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The pleitropic regulator AdpAch is required for natamycin biosynthesis and morphological differentiation in Streptomyces chattanoogensis

Zhou

et al. 2011

Microbiology

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“…These results indicated that both gdmRI and gdmRII were positive regulatory genes of the geldanamycin biosynthesis. AveR [7] , RapH [8] , MonH [9] , PikD [10] , PimR [11] 以及 NysRI 和 NusRII [12] 等, 它们与链霉菌抗生素调控蛋 …”

mentioning

confidence: 99%

Regulatory Genes of Geldanamycin Biosynthesis

Lei

Liu

et al. 2008

Chinese Journal of Biotechnology

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“…Sequencing analysis showed that SanG exhibits significant sequence similarity with PolR, PimR and PteR (Li et al, 2009b;Antó n et al, 2004;Ikeda et al, 2003). All these proteins contain three major functional domains: an OmpR-like DNA-binding domain, a central ATPase domain with a potential ATP-binding motif and a Cterminal half homologous to the guanylate cyclase domain of the LuxR family.…”

Section: Introductionmentioning

confidence: 99%

SanG, a transcriptional activator, controls nikkomycin biosynthesis through binding to the sanN–sanO intergenic region in Streptomyces ansochromogenes

Pan

et al. 2010

Microbiology

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Streptomyces ansochromogenes SanG is a pathway-specific regulator that mainly controls the transcription of two transcriptional units involved in nikkomycin biosynthesis. SanG consists of three major functional domains: an N-terminal Streptomyces antibiotic regulatory protein (SARP) domain, a central ATPase domain, and a C-terminal half homologous to guanylate cyclases belonging to the LuxR family. SanG was expressed in Escherichia coli as a C-terminally His6-tagged protein. The purified SanG-His6 was shown to be a dimer in solution by dynamic light scattering. An electrophoretic mobility-shift assay showed that the purified SanG protein could bind to the DNA fragment containing the bidirectional sanN–sanO promoter region. The SanG-binding sites within the bidirectional sanN–sanO promoter region were determined by footprinting analysis and identified a consensus-directed repeat sequence 5′-CGGCAAG-3′. SanG showed significant ATPase/GTPase activity in vitro, and addition of ATP/GTP enhanced the affinity of SanG for target DNA, but ATP/GTP hydrolysis was not essential for SanG binding to the target DNA. However, real-time reverse transcription PCR showed that mutation of the ATPase/GTPase domain of SanG significantly decreased the transcriptional level of sanN–I and sanO–V. These results indicated that the ATPase/GTPase activity of SanG modulated the transcriptional activation of SanG target genes during nikkomycin biosynthesis.

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Identification of PimR as a Positive Regulator of Pimaricin Biosynthesis in Streptomyces natalensis

Cited by 92 publications

References 41 publications

The pleitropic regulator AdpAch is required for natamycin biosynthesis and morphological differentiation in Streptomyces chattanoogensis

The pleitropic regulator AdpAch is required for natamycin biosynthesis and morphological differentiation in Streptomyces chattanoogensis

Regulatory Genes of Geldanamycin Biosynthesis

SanG, a transcriptional activator, controls nikkomycin biosynthesis through binding to the sanN–sanO intergenic region in Streptomyces ansochromogenes

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