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Jan Kormanec - One of the best experts on this subject based on the ideXlab platform.
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Intriguing properties of the angucycline antibiotic auricin and complex regulation of its biosynthesis
Applied Microbiology and Biotechnology, 2014Co-Authors: Jan Kormanec, Renata Novakova, Erik Mingyar, Lubomira FeckovaAbstract:Streptomyces bacteria are major producers of bioactive natural products, including many antibiotics. We identified a gene cluster, aur1 , in a large linear plasmid of Streptomyces aureofaciens CCM3239. The cluster is responsible for the production of a new angucycline polyketide antibiotic auricin. Several tailoring biosynthetic genes were scatted in rather distant aur1 flanking regions. Auricin was produced in a very narrow growth phase interval of several hours after entry into stationary phase, after which it was degraded to non-active metabolites because of its instability at the high pH values reached after the production stage. Strict transcriptional regulation of the auricin biosynthetic gene cluster has been demonstrated, including feed-forward and feedback control by auricin intermediates via several of the huge number of regulatory genes present in the aur1 cluster. The complex mechanism may ensure strict confinement of auricin production to a specific growth stage.
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a gene determining a new member of the sarp family contributes to transcription of genes for the synthesis of the angucycline polyketide auricin in Streptomyces aureofaciens ccm 3239
Fems Microbiology Letters, 2013Co-Authors: Alena Rehakova, Lubomira Feckova, Renata Novakova, Erik Mingyar, Jan KormanecAbstract:Three regulators, Aur1P, Aur1R and a SARP-family Aur1PR3, have been previously found to control expression of the aur1 cluster for the angucycline antibiotic auricin in Streptomyces aureofaciens CCM 3239. Here, we describe an additional regulatory gene, aur1PR4, encoding a homologue from the SARP-family regulators. Its role in auricin regulation was confirmed by its disruption that dramatically affected auricin production. However, transcription from the aur1Ap promoter, directing expression of 22 auricin biosynthetic genes, was not substantially affected in the Δaur1PR4 mutant. A new promoter, sa13p, directing transcription of four putative auricin tailoring genes, was found to be dependent on aur1PR4. Moreover, analysis of the sa13p promoter region revealed the presence of three heptameric repeat sequences corresponding to putative SARP-binding sites. Expression of aur1PR4 is directed by a single promoter, aur1PR4p, which is induced after entry into stationary phase. Transcription from aur1PR4p was absent in a S. aureofaciens Δaur1P mutant strain, and Aur1P was shown to bind specifically to the aur1PR4p promoter. These results indicate a complex network of regulation of the auricin gene cluster. Both Aur1P and Aur1PR3 are involved in regulation of the core aur1A-U biosynthetic genes, and Aur1PR4 in regulation of putative auricin tailoring genes.
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the gene cluster aur1 for the angucycline antibiotic auricin is located on a large linear plasmid psa3239 in Streptomyces aureofaciens ccm 3239
Fems Microbiology Letters, 2013Co-Authors: Renata Novakova, Lubomira Feckova, Erik Mingyar, Alena Rehakova, Renata Knirschova, Marian Farkasovsky, Jan KormanecAbstract:We previously identified a polyketide synthase gene cluster, aur1, responsible for the production of the angucycline antibiotic auricin in Streptomyces aureofaciens CCM 3239. A sequence analysis of the aur1 flanking regions revealed the presence of several genes encoding proteins homologous to those for Streptomyces linear plasmid replication, partitioning and telomere-binding. Pulse-field gel electrophoresis detected the single, 240-kb linear plasmid, pSA3239, in S. aureofaciens CCM3239. The presence of the auricin cluster in pSA3239 was confirmed by several approaches. In addition to aur1, pSA3239 also carries a large number of regulatory genes, and two gene clusters involved in the production of secondary metabolites: the aur2 cluster for an unknown secondary metabolite and the bpsA cluster for the blue pigment indigoidine.
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genetic manipulation of pathway regulation for overproduction of angucycline like antibiotic auricin in Streptomyces aureofaciens ccm 3239
Folia Microbiologica, 2011Co-Authors: Renata Novakova, Lubomira Feckova, Alena Rehakova, Peter Kutas, Renata Knischova, Jan KormanecAbstract:The polyketide gene cluster aur1 is responsible for the production of the antibiotic auricin in Streptomyces aureofaciens CCM 3239. Auricin production is low and strictly regulated by two regulators, Aur1P and Aur1R. To improve auricin yield, we genetically manipulated S. aureofaciens CCM 3239 strain to overcome this strict regulation. A regulatory region including aur1R, aur1P, aur1O and the target biosynthetic aur1Ap promoter were replaced by the strong constitutive ermEp* promoter. However, auricin production was decreased in such a genetically manipulated strain. In the second strategy we placed the aur1P gene for auricin pathway-specific activator under the control of the ermEp* promoter. The resulting strain has been shown to produce 2.8-fold higher amount of auricin compared with the WT strain.
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the role of the tetr family transcriptional regulator aur1r in negative regulation of the auricin gene cluster in Streptomyces aureofaciens ccm 3239
Microbiology, 2010Co-Authors: Renata Novakova, Lubomira Feckova, Peter Kutas, Jan KormanecAbstract:Two regulatory genes, aur1P and aur1R, have been previously identified upstream of the aur1 polyketide gene cluster involved in biosynthesis of the angucycline-like antibiotic auricin in Streptomyces aureofaciens CCM 3239. The aur1P gene encodes a protein similar to the response regulators of bacterial two-component signal transduction systems and has been shown to specifically activate expression of the auricin biosynthetic genes. The aur1R gene encodes a protein homologous to transcriptional repressors of the TetR family. Here we describe the characterization of the aur1R gene. Expression of the gene is directed by a single promoter, aur1Rp, which is induced just before stationary phase. Disruption of aur1R in S. aureofaciens CCM 3239 had no effect on growth and differentiation. However, the disrupted strain produced more auricin than its parental wild-type S. aureofaciens CCM 3239 strain. Transcription from the aur1Ap and aur1Pp promoters, directing expression of the first biosynthetic gene in the auricin gene cluster and the pathway-specific transcriptional activator, respectively, was increased in the S. aureofaciens CCM 3239 aur1R mutant strain. However, Aur1R was shown to bind specifically only to the aur1Pp promoter in vitro. This binding was abolished by the addition of auricin and/or its intermediates. The results indicate that the Aur1R regulator specifically represses expression of the aur1P gene, which encodes a pathway-specific activator of the auricin biosynthetic gene cluster in S. aureofaciens CCM 3239, and that this repression is relieved by auricin or its intermediates.
Lubomira Feckova - One of the best experts on this subject based on the ideXlab platform.
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a structural analysis of the angucycline like antibiotic auricin from Streptomyces lavendulae subsp lavendulae ccm 3239 revealed its high similarity to griseusins
Antibiotics, 2019Co-Authors: Maria Matulova, Renata Novakova, Lubomira Feckova, Erik Mingyar, Dominika Csolleiova, Martina Zduriencikova, J Sedlak, Vladimir Patoprsty, Vlasta Sasinkova, Iveta UhliarikovaAbstract:We previously identified the aur1 gene cluster in Streptomyces lavendulae subsp. lavendulae CCM 3239 (formerly Streptomyces aureofaciens CCM 3239), which is responsible for the production of the angucycline-like antibiotic auricin (1). Preliminary characterization of 1 revealed that it possesses an aminodeoxyhexose d-forosamine and is active against Gram-positive bacteria. Here we determined the structure of 1, finding that it possesses intriguing structural features, which distinguish it from other known angucyclines. In addition to d-forosamine, compound 1 also contains a unique, highly oxygenated aglycone similar to those of spiroketal pyranonaphthoquinones griseusins. Like several other griseusins, 1 also undergoes methanolysis and displays modest cytotoxicity against several human tumor cell lines. Moreover, the central core of the aur1 cluster is highly similar to the partial gris gene cluster responsible for the biosynthesis of griseusin A and B in both the nature of the encoded proteins and the gene organization.
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complete genome sequence of Streptomyces lavendulae subsp lavendulae ccm 3239 formerly Streptomyces aureofaciens ccm 3239 a producer of the angucycline type antibiotic auricin
Genome Announcements, 2018Co-Authors: Tobias Busche, Dagmar Homerova, Renata Novakova, Arwa Aldilaimi, Lubomira Feckova, Bronislava Rezuchova, Erik Mingyar, Dominika Csolleiova, Carmen Bekeova, Anika WinklerAbstract:Streptomyces lavendulae subsp. lavendulae CCM 3239 produces the angucycline antibiotic auricin and was thought to be the type strain of Streptomyces aureofaciens We report the complete genome sequence of this strain, which consists of a linear chromosome and the linear plasmid pSA3239, and demonstrate it to be S. lavendulae subsp. lavendulae.
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Intriguing properties of the angucycline antibiotic auricin and complex regulation of its biosynthesis
Applied Microbiology and Biotechnology, 2014Co-Authors: Jan Kormanec, Renata Novakova, Erik Mingyar, Lubomira FeckovaAbstract:Streptomyces bacteria are major producers of bioactive natural products, including many antibiotics. We identified a gene cluster, aur1 , in a large linear plasmid of Streptomyces aureofaciens CCM3239. The cluster is responsible for the production of a new angucycline polyketide antibiotic auricin. Several tailoring biosynthetic genes were scatted in rather distant aur1 flanking regions. Auricin was produced in a very narrow growth phase interval of several hours after entry into stationary phase, after which it was degraded to non-active metabolites because of its instability at the high pH values reached after the production stage. Strict transcriptional regulation of the auricin biosynthetic gene cluster has been demonstrated, including feed-forward and feedback control by auricin intermediates via several of the huge number of regulatory genes present in the aur1 cluster. The complex mechanism may ensure strict confinement of auricin production to a specific growth stage.
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a gene determining a new member of the sarp family contributes to transcription of genes for the synthesis of the angucycline polyketide auricin in Streptomyces aureofaciens ccm 3239
Fems Microbiology Letters, 2013Co-Authors: Alena Rehakova, Lubomira Feckova, Renata Novakova, Erik Mingyar, Jan KormanecAbstract:Three regulators, Aur1P, Aur1R and a SARP-family Aur1PR3, have been previously found to control expression of the aur1 cluster for the angucycline antibiotic auricin in Streptomyces aureofaciens CCM 3239. Here, we describe an additional regulatory gene, aur1PR4, encoding a homologue from the SARP-family regulators. Its role in auricin regulation was confirmed by its disruption that dramatically affected auricin production. However, transcription from the aur1Ap promoter, directing expression of 22 auricin biosynthetic genes, was not substantially affected in the Δaur1PR4 mutant. A new promoter, sa13p, directing transcription of four putative auricin tailoring genes, was found to be dependent on aur1PR4. Moreover, analysis of the sa13p promoter region revealed the presence of three heptameric repeat sequences corresponding to putative SARP-binding sites. Expression of aur1PR4 is directed by a single promoter, aur1PR4p, which is induced after entry into stationary phase. Transcription from aur1PR4p was absent in a S. aureofaciens Δaur1P mutant strain, and Aur1P was shown to bind specifically to the aur1PR4p promoter. These results indicate a complex network of regulation of the auricin gene cluster. Both Aur1P and Aur1PR3 are involved in regulation of the core aur1A-U biosynthetic genes, and Aur1PR4 in regulation of putative auricin tailoring genes.
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the gene cluster aur1 for the angucycline antibiotic auricin is located on a large linear plasmid psa3239 in Streptomyces aureofaciens ccm 3239
Fems Microbiology Letters, 2013Co-Authors: Renata Novakova, Lubomira Feckova, Erik Mingyar, Alena Rehakova, Renata Knirschova, Marian Farkasovsky, Jan KormanecAbstract:We previously identified a polyketide synthase gene cluster, aur1, responsible for the production of the angucycline antibiotic auricin in Streptomyces aureofaciens CCM 3239. A sequence analysis of the aur1 flanking regions revealed the presence of several genes encoding proteins homologous to those for Streptomyces linear plasmid replication, partitioning and telomere-binding. Pulse-field gel electrophoresis detected the single, 240-kb linear plasmid, pSA3239, in S. aureofaciens CCM3239. The presence of the auricin cluster in pSA3239 was confirmed by several approaches. In addition to aur1, pSA3239 also carries a large number of regulatory genes, and two gene clusters involved in the production of secondary metabolites: the aur2 cluster for an unknown secondary metabolite and the bpsA cluster for the blue pigment indigoidine.
Renata Novakova - One of the best experts on this subject based on the ideXlab platform.
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a structural analysis of the angucycline like antibiotic auricin from Streptomyces lavendulae subsp lavendulae ccm 3239 revealed its high similarity to griseusins
Antibiotics, 2019Co-Authors: Maria Matulova, Renata Novakova, Lubomira Feckova, Erik Mingyar, Dominika Csolleiova, Martina Zduriencikova, J Sedlak, Vladimir Patoprsty, Vlasta Sasinkova, Iveta UhliarikovaAbstract:We previously identified the aur1 gene cluster in Streptomyces lavendulae subsp. lavendulae CCM 3239 (formerly Streptomyces aureofaciens CCM 3239), which is responsible for the production of the angucycline-like antibiotic auricin (1). Preliminary characterization of 1 revealed that it possesses an aminodeoxyhexose d-forosamine and is active against Gram-positive bacteria. Here we determined the structure of 1, finding that it possesses intriguing structural features, which distinguish it from other known angucyclines. In addition to d-forosamine, compound 1 also contains a unique, highly oxygenated aglycone similar to those of spiroketal pyranonaphthoquinones griseusins. Like several other griseusins, 1 also undergoes methanolysis and displays modest cytotoxicity against several human tumor cell lines. Moreover, the central core of the aur1 cluster is highly similar to the partial gris gene cluster responsible for the biosynthesis of griseusin A and B in both the nature of the encoded proteins and the gene organization.
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complete genome sequence of Streptomyces lavendulae subsp lavendulae ccm 3239 formerly Streptomyces aureofaciens ccm 3239 a producer of the angucycline type antibiotic auricin
Genome Announcements, 2018Co-Authors: Tobias Busche, Dagmar Homerova, Renata Novakova, Arwa Aldilaimi, Lubomira Feckova, Bronislava Rezuchova, Erik Mingyar, Dominika Csolleiova, Carmen Bekeova, Anika WinklerAbstract:Streptomyces lavendulae subsp. lavendulae CCM 3239 produces the angucycline antibiotic auricin and was thought to be the type strain of Streptomyces aureofaciens We report the complete genome sequence of this strain, which consists of a linear chromosome and the linear plasmid pSA3239, and demonstrate it to be S. lavendulae subsp. lavendulae.
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Intriguing properties of the angucycline antibiotic auricin and complex regulation of its biosynthesis
Applied Microbiology and Biotechnology, 2014Co-Authors: Jan Kormanec, Renata Novakova, Erik Mingyar, Lubomira FeckovaAbstract:Streptomyces bacteria are major producers of bioactive natural products, including many antibiotics. We identified a gene cluster, aur1 , in a large linear plasmid of Streptomyces aureofaciens CCM3239. The cluster is responsible for the production of a new angucycline polyketide antibiotic auricin. Several tailoring biosynthetic genes were scatted in rather distant aur1 flanking regions. Auricin was produced in a very narrow growth phase interval of several hours after entry into stationary phase, after which it was degraded to non-active metabolites because of its instability at the high pH values reached after the production stage. Strict transcriptional regulation of the auricin biosynthetic gene cluster has been demonstrated, including feed-forward and feedback control by auricin intermediates via several of the huge number of regulatory genes present in the aur1 cluster. The complex mechanism may ensure strict confinement of auricin production to a specific growth stage.
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a gene determining a new member of the sarp family contributes to transcription of genes for the synthesis of the angucycline polyketide auricin in Streptomyces aureofaciens ccm 3239
Fems Microbiology Letters, 2013Co-Authors: Alena Rehakova, Lubomira Feckova, Renata Novakova, Erik Mingyar, Jan KormanecAbstract:Three regulators, Aur1P, Aur1R and a SARP-family Aur1PR3, have been previously found to control expression of the aur1 cluster for the angucycline antibiotic auricin in Streptomyces aureofaciens CCM 3239. Here, we describe an additional regulatory gene, aur1PR4, encoding a homologue from the SARP-family regulators. Its role in auricin regulation was confirmed by its disruption that dramatically affected auricin production. However, transcription from the aur1Ap promoter, directing expression of 22 auricin biosynthetic genes, was not substantially affected in the Δaur1PR4 mutant. A new promoter, sa13p, directing transcription of four putative auricin tailoring genes, was found to be dependent on aur1PR4. Moreover, analysis of the sa13p promoter region revealed the presence of three heptameric repeat sequences corresponding to putative SARP-binding sites. Expression of aur1PR4 is directed by a single promoter, aur1PR4p, which is induced after entry into stationary phase. Transcription from aur1PR4p was absent in a S. aureofaciens Δaur1P mutant strain, and Aur1P was shown to bind specifically to the aur1PR4p promoter. These results indicate a complex network of regulation of the auricin gene cluster. Both Aur1P and Aur1PR3 are involved in regulation of the core aur1A-U biosynthetic genes, and Aur1PR4 in regulation of putative auricin tailoring genes.
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the gene cluster aur1 for the angucycline antibiotic auricin is located on a large linear plasmid psa3239 in Streptomyces aureofaciens ccm 3239
Fems Microbiology Letters, 2013Co-Authors: Renata Novakova, Lubomira Feckova, Erik Mingyar, Alena Rehakova, Renata Knirschova, Marian Farkasovsky, Jan KormanecAbstract:We previously identified a polyketide synthase gene cluster, aur1, responsible for the production of the angucycline antibiotic auricin in Streptomyces aureofaciens CCM 3239. A sequence analysis of the aur1 flanking regions revealed the presence of several genes encoding proteins homologous to those for Streptomyces linear plasmid replication, partitioning and telomere-binding. Pulse-field gel electrophoresis detected the single, 240-kb linear plasmid, pSA3239, in S. aureofaciens CCM3239. The presence of the auricin cluster in pSA3239 was confirmed by several approaches. In addition to aur1, pSA3239 also carries a large number of regulatory genes, and two gene clusters involved in the production of secondary metabolites: the aur2 cluster for an unknown secondary metabolite and the bpsA cluster for the blue pigment indigoidine.
Dagmar Homerova - One of the best experts on this subject based on the ideXlab platform.
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complete genome sequence of Streptomyces lavendulae subsp lavendulae ccm 3239 formerly Streptomyces aureofaciens ccm 3239 a producer of the angucycline type antibiotic auricin
Genome Announcements, 2018Co-Authors: Tobias Busche, Dagmar Homerova, Renata Novakova, Arwa Aldilaimi, Lubomira Feckova, Bronislava Rezuchova, Erik Mingyar, Dominika Csolleiova, Carmen Bekeova, Anika WinklerAbstract:Streptomyces lavendulae subsp. lavendulae CCM 3239 produces the angucycline antibiotic auricin and was thought to be the type strain of Streptomyces aureofaciens We report the complete genome sequence of this strain, which consists of a linear chromosome and the linear plasmid pSA3239, and demonstrate it to be S. lavendulae subsp. lavendulae.
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characterization of a regulatory gene essential for the production of the angucycline like polyketide antibiotic auricin in Streptomyces aureofaciens ccm 3239
Microbiology, 2005Co-Authors: Renata Novakova, Dagmar Homerova, Lubomira Feckova, Jan KormanecAbstract:A gene, aur1P, encoding a protein similar to the response regulators of bacterial two-component signal transduction systems, was identified upstream of the aur1 polyketide gene cluster involved in biosynthesis of the angucycline-like antibiotic auricin in Streptomyces aureofaciens CCM 3239. Expression of the gene was directed by a single promoter, aur1Pp, which was transcribed at low levels during the exponential phase and induced just before the stationary phase. A divergently transcribed gene, aur1R, has been identified upstream of aur1P, encoding a protein homologous to transcriptional repressors of the TetR family. The aur1P gene was disrupted in the S. aureofaciens CCM 3239 chromosome by homologous recombination. The mutation in the aur1P gene had no effect on growth and differentiation. However, biochromatographic analysis of culture extracts from the S. aureofaciens aur1P-disrupted strain revealed that auricin was not produced in the mutant. This indicated that aur1P is essential for auricin production. Transcription from the previously characterized aur1Ap promoter, directing expression of the first gene, aur1A, in the auricin gene cluster, was dramatically decreased in the S. aureofaciens CCM 3239 aur1P mutant strain. Moreover, the Aur1P protein, overproduced in Escherichia coli, was shown to bind specifically upstream of the aur1Ap promoter region. The results indicated that the Aur1P regulator activates expression of the auricin biosynthesis genes.
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cloning and characterization of a polyketide synthase gene cluster involved in biosynthesis of a proposed angucycline like polyketide auricin in Streptomyces aureofaciens ccm 3239
Gene, 2002Co-Authors: Renata Novakova, Dagmar Homerova, Bronislava Rezuchova, Jana Bistakova, Jan KormanecAbstract:A new polyketide gene cluster, aur1, was identified in Streptomyces aureofaciens CCM3239 by using genes for the spore-pigment polyketide synthase of the Streptomyces coelicolor whiE operon as a probe. Sequence analysis of three overlapping DNA fragments (encompassing 15,100 bp) revealed 15 open reading frames, the majority of which showed high similarity to the previously characterized type II polyketide synthase genes. The highest similarity was to three Streptomyces polyketide gene clusters involved in biosynthesis of angucycline antibiotics, jadomycin, urdamycin and landomycin. The proposed S. aureofaciens ketosynthase (Aur1D) was phylogenetically more related to all known ketosynthases for polyketide antibiotics in Streptomyces than to spore-pigment ketosynthases. Interestingly, the aur1 gene cluster contained a gene encoding a proposed malonyl-CoA:ACP transacylase that has not been identified in any of the previously characterized type II polyketide synthase cluster. Transcriptional analysis of aur1 revealed a single promoter upstream the first open reading frame (the aur1A gene) that was active in all stages of differentiation with increased activity at the time of aerial mycelium formation. The aur1 gene cluster was disrupted by a homologous recombination, replacing the three genes (aur1B,C,D) including ketosynthase, with antibiotic resistance marker gene in S. aureofaciens chromosome. Disruption did not affect growth and differentiation; disrupted strain produced spores with wild-type gray-pink pigmentation. The biochromatographic analysis of the culture extracts from S. aureofaciens wild-type and aur1-disrupted strains revealed an antibacterial compound that was missing in the mutant. The results indicated a role of the S. aureofaciens aur1 gene cluster in biosynthesis of a polyketide secondary metabolite (which we named auricin), and not in the spore pigment biosynthesis.
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disruption of a glycogen branching enzyme gene glgb specifically affects the sporulation associated phase of glycogen accumulation in Streptomyces aureofaciens
Microbiology, 1996Co-Authors: Dagmar Homerova, Oldŗich Benada, Olga Kofroňova, Bronislava ŗežuchova, Jan KormanecAbstract:In the course of Streptomyces differentiation, glycogen is accumulated in two discrete phases: in substrate hyphae that undergo aerial mycelium formation (phase I), and during septation of aerial hyphae (phase II). We have disrupted a previously identified gene, glgB, encoding a putative glycogen-branching enzyme in Streptomyces aureofaciens. Disruption of the gene had no profound effect on sporulation. However, the amount of glycogen-like polysaccharides, compared to wild-type (WT) S. aureofaciens, decreased in the late stage of differentiation of the glgB-disrupted strain. Absorption spectra of polysaccharides extracted from the WT and glgB-disrupted strains have shown the presence of glycogen in both strains in the first stage of differentiation (aerial mycelium formation), and unbranched glucan was detected in the glgB-disrupted strain in the late stage of differentiation. The results were confirmed by electron microscopy after silver proteinate staining of glycogen granules. Two distinct glycogen-branching enzymes, which had temporally different expression during differentiation, were detected in WT S. aureofaciens. The absence of this enzyme activity in the late stage of differentiation in the glgB mutant suggests that the product of the glgB gene is responsible for phase II glycogen accumulation.
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cloning of the putative glycogen branching enzyme gene glgb from Streptomyces aureofaciens
Biochimica et Biophysica Acta, 1994Co-Authors: Dagmar Homerova, Jan KormanecAbstract:Abstract The complete nucleotide sequence of a gene, glgB, encoding a putative glycogen branching enzyme from Streptomyces aureofaciens has been determined. The deduced protein of 764 amino acids with an Mr of 85 292 shows high similarity to the all bacterial glycogen branching enzymes (43% to 49% amino acid identity), and shares all conserved domains of this group of enzymes.
Erik Mingyar - One of the best experts on this subject based on the ideXlab platform.
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a structural analysis of the angucycline like antibiotic auricin from Streptomyces lavendulae subsp lavendulae ccm 3239 revealed its high similarity to griseusins
Antibiotics, 2019Co-Authors: Maria Matulova, Renata Novakova, Lubomira Feckova, Erik Mingyar, Dominika Csolleiova, Martina Zduriencikova, J Sedlak, Vladimir Patoprsty, Vlasta Sasinkova, Iveta UhliarikovaAbstract:We previously identified the aur1 gene cluster in Streptomyces lavendulae subsp. lavendulae CCM 3239 (formerly Streptomyces aureofaciens CCM 3239), which is responsible for the production of the angucycline-like antibiotic auricin (1). Preliminary characterization of 1 revealed that it possesses an aminodeoxyhexose d-forosamine and is active against Gram-positive bacteria. Here we determined the structure of 1, finding that it possesses intriguing structural features, which distinguish it from other known angucyclines. In addition to d-forosamine, compound 1 also contains a unique, highly oxygenated aglycone similar to those of spiroketal pyranonaphthoquinones griseusins. Like several other griseusins, 1 also undergoes methanolysis and displays modest cytotoxicity against several human tumor cell lines. Moreover, the central core of the aur1 cluster is highly similar to the partial gris gene cluster responsible for the biosynthesis of griseusin A and B in both the nature of the encoded proteins and the gene organization.
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complete genome sequence of Streptomyces lavendulae subsp lavendulae ccm 3239 formerly Streptomyces aureofaciens ccm 3239 a producer of the angucycline type antibiotic auricin
Genome Announcements, 2018Co-Authors: Tobias Busche, Dagmar Homerova, Renata Novakova, Arwa Aldilaimi, Lubomira Feckova, Bronislava Rezuchova, Erik Mingyar, Dominika Csolleiova, Carmen Bekeova, Anika WinklerAbstract:Streptomyces lavendulae subsp. lavendulae CCM 3239 produces the angucycline antibiotic auricin and was thought to be the type strain of Streptomyces aureofaciens We report the complete genome sequence of this strain, which consists of a linear chromosome and the linear plasmid pSA3239, and demonstrate it to be S. lavendulae subsp. lavendulae.
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Intriguing properties of the angucycline antibiotic auricin and complex regulation of its biosynthesis
Applied Microbiology and Biotechnology, 2014Co-Authors: Jan Kormanec, Renata Novakova, Erik Mingyar, Lubomira FeckovaAbstract:Streptomyces bacteria are major producers of bioactive natural products, including many antibiotics. We identified a gene cluster, aur1 , in a large linear plasmid of Streptomyces aureofaciens CCM3239. The cluster is responsible for the production of a new angucycline polyketide antibiotic auricin. Several tailoring biosynthetic genes were scatted in rather distant aur1 flanking regions. Auricin was produced in a very narrow growth phase interval of several hours after entry into stationary phase, after which it was degraded to non-active metabolites because of its instability at the high pH values reached after the production stage. Strict transcriptional regulation of the auricin biosynthetic gene cluster has been demonstrated, including feed-forward and feedback control by auricin intermediates via several of the huge number of regulatory genes present in the aur1 cluster. The complex mechanism may ensure strict confinement of auricin production to a specific growth stage.
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a gene determining a new member of the sarp family contributes to transcription of genes for the synthesis of the angucycline polyketide auricin in Streptomyces aureofaciens ccm 3239
Fems Microbiology Letters, 2013Co-Authors: Alena Rehakova, Lubomira Feckova, Renata Novakova, Erik Mingyar, Jan KormanecAbstract:Three regulators, Aur1P, Aur1R and a SARP-family Aur1PR3, have been previously found to control expression of the aur1 cluster for the angucycline antibiotic auricin in Streptomyces aureofaciens CCM 3239. Here, we describe an additional regulatory gene, aur1PR4, encoding a homologue from the SARP-family regulators. Its role in auricin regulation was confirmed by its disruption that dramatically affected auricin production. However, transcription from the aur1Ap promoter, directing expression of 22 auricin biosynthetic genes, was not substantially affected in the Δaur1PR4 mutant. A new promoter, sa13p, directing transcription of four putative auricin tailoring genes, was found to be dependent on aur1PR4. Moreover, analysis of the sa13p promoter region revealed the presence of three heptameric repeat sequences corresponding to putative SARP-binding sites. Expression of aur1PR4 is directed by a single promoter, aur1PR4p, which is induced after entry into stationary phase. Transcription from aur1PR4p was absent in a S. aureofaciens Δaur1P mutant strain, and Aur1P was shown to bind specifically to the aur1PR4p promoter. These results indicate a complex network of regulation of the auricin gene cluster. Both Aur1P and Aur1PR3 are involved in regulation of the core aur1A-U biosynthetic genes, and Aur1PR4 in regulation of putative auricin tailoring genes.
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the gene cluster aur1 for the angucycline antibiotic auricin is located on a large linear plasmid psa3239 in Streptomyces aureofaciens ccm 3239
Fems Microbiology Letters, 2013Co-Authors: Renata Novakova, Lubomira Feckova, Erik Mingyar, Alena Rehakova, Renata Knirschova, Marian Farkasovsky, Jan KormanecAbstract:We previously identified a polyketide synthase gene cluster, aur1, responsible for the production of the angucycline antibiotic auricin in Streptomyces aureofaciens CCM 3239. A sequence analysis of the aur1 flanking regions revealed the presence of several genes encoding proteins homologous to those for Streptomyces linear plasmid replication, partitioning and telomere-binding. Pulse-field gel electrophoresis detected the single, 240-kb linear plasmid, pSA3239, in S. aureofaciens CCM3239. The presence of the auricin cluster in pSA3239 was confirmed by several approaches. In addition to aur1, pSA3239 also carries a large number of regulatory genes, and two gene clusters involved in the production of secondary metabolites: the aur2 cluster for an unknown secondary metabolite and the bpsA cluster for the blue pigment indigoidine.