PimM, a PAS domain positive regulator of pimaricin biosynthesis in Streptomyces natalensis

Antón, Nuria; Santos‐Aberturas, Javier; Mendes, Marta V.; Guerra, Susana; Martı́n, Juan F.; Aparicio, Jesús F.

doi:10.1099/mic.0.2007/009126-0

Cited by 87 publications

(89 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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: 52%

“…This change seems to provide a more economical way for the host to control and initiate the production of NTM, since fewer ScnRII molecules are needed. Since increasing the gene dosage of scnRII or pimM could enhance NTM prodution (Antó n et al, 2007;Du et al, 2009), it is an interesting hypothesis to think about an enhanced NTM yield for the scn cluster compared with the pim cluster. Up to now, the evolutionary analysis of antibiotic gene clusters has mainly focused on the phylogenetic analysis of synthases such as polyketide synthase (PKS) and NRPS; our research provides new insights into the evolution and distribution of these gene clusters.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…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%

See 3 more Smart Citations

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

Zhou

et al. 2011

Microbiology

View full text Add to dashboard Cite

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.

show abstract

Section: Resultscontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Zhou

et al. 2011

Microbiology

View full text Add to dashboard Cite

show abstract

“…、纳塔尔链霉菌(Streptomyces natalensis) [3] 和恰塔努加链霉菌 (Streptomyces chatanoogensis) [4] 发酵生产。目前我国主要利用褐黄孢链霉菌 se surface methodology.…”

unclassified

High Efficient Fermentation of Natamycin with Streptomyces Gilvosporeus HBJ591

宋慧婷¹,

邓锐²,

江正兵³

2012

View full text Add to dashboard Cite

Based on the study of sugar supplement process, high efficient fermentation with Streptomyces gilvosporeus HBJ591 was carried out via the optimization of the fermentation medium. When the reducing sugar concentration in the fermenter was 2.5%, the synthetic course of natamycin was extended effectively. Response surface method was used to optimize the fermention medium of HBJ591, then fed-batch fermentation was carried out in 16 L fermenter, the natamycin fermentation level reached 15.7 g/L, and the highest yield was 4.8 times higher than the original process.

show abstract

Genome Mining of the Biosynthetic Gene Cluster of the Polyene Macrolide Antibiotic Tetramycin and Characterization of a P450 Monooxygenase Involved in the Hydroxylation of the Tetramycin B Polyol Segment

et al. 2012

View full text Add to dashboard Cite

A polyene macrolide antibiotic tetramycin biosynthetic gene cluster was identified by genome mining and isolated from Streptomyces hygrospinosus var. beijingensis. Genetic and in silico analyses gave insights into the mechanism of biosynthesis of tetramycin, and a model of the tetramycin biosynthetic pathway is proposed. Inactivation of a cytochrome P450 monooxygenase gene, tetrK, resulted in the production of a tetramycin B precursor: tetramycin A, which lacks a hydroxy group in its polyol region. TetrK was subsequently overexpressed heterologously in E. coli with a His(6) tag, and purified TetrK efficiently hydroxylated tetramycin A to afford tetramycin B. Kinetic studies revealed no inhibition of TetrK by substrate or product. Surprisingly, sequence-alignment analysis showed that TetrK, as a hydroxylase, has much higher homology with epoxidase PimD than with hydroxylases NysL and AmphL. The 3D structure of TetrK was then constructed by homology modeling with PimD as reference. Although TetrK and PimD catalyzed different chemical reactions, homology modeling indicated that they might share the same catalytic sites, despite also possessing some different sites correlated with substrate binding and substrate specificity. These findings offer good prospects for the production of improved antifungal polyene analogues.

show abstract

PimM, a PAS domain positive regulator of pimaricin biosynthesis in Streptomyces natalensis

Cited by 87 publications

References 35 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

High Efficient Fermentation of Natamycin with Streptomyces Gilvosporeus HBJ591

Genome Mining of the Biosynthetic Gene Cluster of the Polyene Macrolide Antibiotic Tetramycin and Characterization of a P450 Monooxygenase Involved in the Hydroxylation of the Tetramycin B Polyol Segment

Contact Info

Product

Resources

About