The Experts below are selected from a list of 7917 Experts worldwide ranked by ideXlab platform
Ying Wen - One of the best experts on this subject based on the ideXlab platform.
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Avermectins, intelligently made in China
Yi chuan = Hereditas, 2018Co-Authors: Ying Wen, Lixin ZhangAbstract:Avermectins, are pesticides of fermentation products with high efficacy and low toxicity and play important roles in food and agricultural product safety, animal and human health. Ivermectins, the derivatives of Avermectins, are used to treat Onchocerciasis, also known as River Blindness. Thanks to these discoveries, more than 200 million Africans are lucky to be exempted from blindness. Great efforts have been made on better understanding of the microbial production system of Avermectins through genetic engineering in China. Starting from scratch, Chinese Avermectin industry has experienced a comprehensive technological innovation with significantly improved yield, titer and productivity of Avermectins, and became the exclusive supplier for the global market. The success of Avermectin industry innovation in China not only shed lights on the intelligent yield improvement of other microbial natural product drugs, but also gained wide international recognition. We provide here an overview of the discovery and development of basic and applied research of Avermectins, especially historical evolution of Avermectins made in China, which will benefit industrial development of microbial drugs in China.
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Data_Sheet_1_Organic Peroxide-Sensing Repressor OhrR Regulates Organic Hydroperoxide Stress Resistance and Avermectin Production in Streptomyces avermitilis.PDF
2018Co-Authors: Meng Sun, Ying Wen, Yuan Song, Mengya Lyu, Zhi ChenAbstract:The bacterium Streptomyces avermitilis is an industrial-scale producer of Avermectins, which are important anthelmintic agents widely used in agriculture, veterinary medicine, and human medicine. During the Avermectin fermentation process, S. avermitilis is exposed to organic peroxides generated by aerobic respiration. We investigated the role of MarR-family transcriptional regulator OhrR in oxidative stress response and Avermectin production in S. avermitilis. The S. avermitilis genome encodes two organic hydroperoxide resistance proteins: OhrB1 and OhrB2. OhrB2 is the major resistance protein in organic peroxide stress responses. In the absence of organic peroxide, the reduced form of OhrR represses the expression of ohrB2 gene by binding to the OhrR box in the promoter region. In the presence of organic peroxide, the oxidized form of OhrR dissociates from the OhrR box and the expression of ohrB2 is increased by derepression. OhrR also acts as a repressor to regulate its own expression. An ohrR-deletion mutant (termed DohrR) displayed enhanced Avermectin production. Our findings demonstrate that OhrR in S. avermitilis represses Avermectin production by regulating the expression of pathway-specific regulatory gene aveR. OhrR also plays a regulatory role in glycolysis and the pentose phosphate (PP) pathway by negatively controlling the expression of pykA2 and ctaB/tkt2-tal2-zwf2-opcA2-pgl.
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sav742 a novel arac family regulator from streptomyces avermitilis controls Avermectin biosynthesis cell growth and development
Scientific Reports, 2016Co-Authors: Di Sun, Zhi Chen, Jianya Zhu, Ying WenAbstract:Avermectins are useful anthelmintic antibiotics produced by Streptomyces avermitilis. We demonstrated that a novel AraC-family transcriptional regulator in this species, SAV742, is a global regulator that negatively controls Avermectin biosynthesis and cell growth, but positively controls morphological differentiation. Deletion of its gene, sav_742, increased Avermectin production and dry cell weight, but caused delayed formation of aerial hyphae and spores. SAV742 directly inhibited Avermectin production by repressing transcription of ave structural genes, and also directly regulated its own gene (sav_742) and adjacent gene sig8 (sav_741). The precise SAV742-binding site on its own promoter region was determined by DNase I footprinting assay coupled with site-directed DNA mutagenesis, and 5-nt inverted repeats (GCCGA-n10/n12-TCGGC) were found to be essential for SAV742 binding. Similar 5-nt inverted repeats separated by 3, 10 or 15 nt were found in the promoter regions of target ave genes and sig8. The SAV742 regulon was predicted based on bioinformatic analysis. Twenty-six new SAV742 targets were identified and experimentally confirmed, including genes involved in primary metabolism, secondary metabolism and development. Our findings indicate that SAV742 plays crucial roles in not only Avermectin biosynthesis but also coordination of complex physiological processes in S. avermitilis.
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increasing Avermectin production in streptomyces avermitilis by manipulating the expression of a novel tetr family regulator and its target gene product
Applied and Environmental Microbiology, 2015Co-Authors: Wenshuai Liu, Zhi Chen, Jia Guo, Qinling Zhang, Ying WenAbstract:ABSTRACT Avermectins produced by Streptomyces avermitilis are commercially important anthelmintic agents. The detailed regulatory mechanisms of Avermectin biosynthesis remain unclear. Here, we identified SAV3619, a TetR-family transcriptional regulator designated AveT, to be an activator for both Avermectin production and morphological differentiation in S. avermitilis. AveT was shown to indirectly stimulate Avermectin production by affecting transcription of the cluster-situated activator gene aveR . AveT directly repressed transcription of its own gene ( aveT ), adjacent gene pepD2 ( sav_3620 ), sav_7490 (designated aveM ), and sav_7491 by binding to an 18-bp perfect palindromic sequence (CGAAACGKTKYCGTTTCG, where K is T or G and Y is T or C and where the underlining indicates inverted repeats) within their promoter regions. aveM (which encodes a putative transmembrane efflux protein belonging to the major facilitator superfamily [MFS]), the important target gene of AveT, had a striking negative effect on Avermectin production and morphological differentiation. Overexpression of aveT and deletion of aveM in wild-type and industrial strains of S. avermitilis led to clear increases in the levels of Avermectin production. In vitro gel-shift assays suggested that C-5–O-B1, the late pathway precursor of Avermectin B1, acts as an AveT ligand. Taken together, our findings indicate positive-feedback regulation of aveT expression and Avermectin production by a late pathway intermediate and provide the basis for an efficient strategy to increase Avermectin production in S. avermitilis by manipulation of AveT and its target gene product, AveM.
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two adjacent and similar tetr family transcriptional regulator genes sav577 and sav576 co regulate Avermectin production in streptomyces avermitilis
PLOS ONE, 2014Co-Authors: Jia Guo, Xuan Zhang, Zhi Chen, Ying WenAbstract:Streptomyces avermitilis is an important bacterial species used for industrial production of Avermectins, a family of broad-spectrum anthelmintic agents. We previously identified the protein SAV576, a TetR family transcriptional regulator (TFR), as a downregulator of Avermectin biosynthesis that acts by controlling transcription of its major target gene SAV575 (which encodes cytochrome P450/NADPH-ferrihemoprotein reductase) and ave genes. SAV577, another TFR gene, encodes a SAV577 protein that displays high amino acid homology with SAV576. In this study, we examined the effect of SAV577 on Avermectin production and the relationships between SAV576 and SAV577. SAV577 downregulated Avermectin biosynthesis indirectly, similarly to SAV576. SAV576 and SAV577 both directly repressed SAV575 transcription, and reciprocally repressed each other's expression. SAV575 transcription levels in various S. avermitilis strains were correlated with Avermectin production levels. DNase I footprinting and electrophoretic mobility shift assays indicated that SAV576 and SAV577 compete for the same binding regions, and that DNA-binding affinity of SAV576 is much stronger than that of SAV577. GST pull-down assays revealed no direct interaction between the two proteins. Taken together, these findings suggest that SAV577 regulates Avermectin production in S. avermitilis by a mechanism similar to that of SAV576, and that the role of SAV576 is dominant over that of SAV577. This is the first report of two adjacent and similar TFR genes that co-regulate antibiotic production in Streptomyces.
Zhi Chen - One of the best experts on this subject based on the ideXlab platform.
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Organic Peroxide-Sensing Repressor OhrR Regulates Organic Hydroperoxide Stress Resistance and Avermectin Production in Streptomyces avermitilis.
Frontiers in Microbiology, 2018Co-Authors: Yuan Song, Jilun Li, Zhi ChenAbstract:The bacterium Streptomyces avermitilis is an industrial-scale producer of Avermectins, which are important anthelmintic agents widely used in agriculture, veterinary medicine, and human medicine. During the Avermectin fermentation process, S. avermitilis is exposed to organic peroxides generated by aerobic respiration. We investigated the role of MarR-family transcriptional regulator OhrR in oxidative stress response and Avermectin production in S. avermitilis. The S. avermitilis genome encodes two organic hydroperoxide resistance proteins: OhrB1 and OhrB2. OhrB2 is the major resistance protein in organic peroxide stress responses. In the absence of organic peroxide, the reduced form of OhrR represses the expression of ohrB2 gene by binding to the OhrR box in the promoter region. In the presence of organic peroxide, the oxidized form of OhrR dissociates from the OhrR box and the expression of ohrB2 is increased by derepression. OhrR also acts as a repressor to regulate its own expression. An ohrR-deletion mutant (termed DohrR) displayed enhanced Avermectin production. Our findings demonstrate that OhrR in S. avermitilis represses Avermectin production by regulating the expression of pathway-specific regulatory gene aveR. OhrR also plays a regulatory role in glycolysis and the pentose phosphate (PP) pathway by negatively controlling the expression of pykA2 and ctaB/tkt2-tal2-zwf2-opcA2-pgl.
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Data_Sheet_1_Organic Peroxide-Sensing Repressor OhrR Regulates Organic Hydroperoxide Stress Resistance and Avermectin Production in Streptomyces avermitilis.PDF
2018Co-Authors: Meng Sun, Ying Wen, Yuan Song, Mengya Lyu, Zhi ChenAbstract:The bacterium Streptomyces avermitilis is an industrial-scale producer of Avermectins, which are important anthelmintic agents widely used in agriculture, veterinary medicine, and human medicine. During the Avermectin fermentation process, S. avermitilis is exposed to organic peroxides generated by aerobic respiration. We investigated the role of MarR-family transcriptional regulator OhrR in oxidative stress response and Avermectin production in S. avermitilis. The S. avermitilis genome encodes two organic hydroperoxide resistance proteins: OhrB1 and OhrB2. OhrB2 is the major resistance protein in organic peroxide stress responses. In the absence of organic peroxide, the reduced form of OhrR represses the expression of ohrB2 gene by binding to the OhrR box in the promoter region. In the presence of organic peroxide, the oxidized form of OhrR dissociates from the OhrR box and the expression of ohrB2 is increased by derepression. OhrR also acts as a repressor to regulate its own expression. An ohrR-deletion mutant (termed DohrR) displayed enhanced Avermectin production. Our findings demonstrate that OhrR in S. avermitilis represses Avermectin production by regulating the expression of pathway-specific regulatory gene aveR. OhrR also plays a regulatory role in glycolysis and the pentose phosphate (PP) pathway by negatively controlling the expression of pykA2 and ctaB/tkt2-tal2-zwf2-opcA2-pgl.
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sav742 a novel arac family regulator from streptomyces avermitilis controls Avermectin biosynthesis cell growth and development
Scientific Reports, 2016Co-Authors: Di Sun, Zhi Chen, Jianya Zhu, Ying WenAbstract:Avermectins are useful anthelmintic antibiotics produced by Streptomyces avermitilis. We demonstrated that a novel AraC-family transcriptional regulator in this species, SAV742, is a global regulator that negatively controls Avermectin biosynthesis and cell growth, but positively controls morphological differentiation. Deletion of its gene, sav_742, increased Avermectin production and dry cell weight, but caused delayed formation of aerial hyphae and spores. SAV742 directly inhibited Avermectin production by repressing transcription of ave structural genes, and also directly regulated its own gene (sav_742) and adjacent gene sig8 (sav_741). The precise SAV742-binding site on its own promoter region was determined by DNase I footprinting assay coupled with site-directed DNA mutagenesis, and 5-nt inverted repeats (GCCGA-n10/n12-TCGGC) were found to be essential for SAV742 binding. Similar 5-nt inverted repeats separated by 3, 10 or 15 nt were found in the promoter regions of target ave genes and sig8. The SAV742 regulon was predicted based on bioinformatic analysis. Twenty-six new SAV742 targets were identified and experimentally confirmed, including genes involved in primary metabolism, secondary metabolism and development. Our findings indicate that SAV742 plays crucial roles in not only Avermectin biosynthesis but also coordination of complex physiological processes in S. avermitilis.
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increasing Avermectin production in streptomyces avermitilis by manipulating the expression of a novel tetr family regulator and its target gene product
Applied and Environmental Microbiology, 2015Co-Authors: Wenshuai Liu, Zhi Chen, Jia Guo, Qinling Zhang, Ying WenAbstract:ABSTRACT Avermectins produced by Streptomyces avermitilis are commercially important anthelmintic agents. The detailed regulatory mechanisms of Avermectin biosynthesis remain unclear. Here, we identified SAV3619, a TetR-family transcriptional regulator designated AveT, to be an activator for both Avermectin production and morphological differentiation in S. avermitilis. AveT was shown to indirectly stimulate Avermectin production by affecting transcription of the cluster-situated activator gene aveR . AveT directly repressed transcription of its own gene ( aveT ), adjacent gene pepD2 ( sav_3620 ), sav_7490 (designated aveM ), and sav_7491 by binding to an 18-bp perfect palindromic sequence (CGAAACGKTKYCGTTTCG, where K is T or G and Y is T or C and where the underlining indicates inverted repeats) within their promoter regions. aveM (which encodes a putative transmembrane efflux protein belonging to the major facilitator superfamily [MFS]), the important target gene of AveT, had a striking negative effect on Avermectin production and morphological differentiation. Overexpression of aveT and deletion of aveM in wild-type and industrial strains of S. avermitilis led to clear increases in the levels of Avermectin production. In vitro gel-shift assays suggested that C-5–O-B1, the late pathway precursor of Avermectin B1, acts as an AveT ligand. Taken together, our findings indicate positive-feedback regulation of aveT expression and Avermectin production by a late pathway intermediate and provide the basis for an efficient strategy to increase Avermectin production in S. avermitilis by manipulation of AveT and its target gene product, AveM.
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two adjacent and similar tetr family transcriptional regulator genes sav577 and sav576 co regulate Avermectin production in streptomyces avermitilis
PLOS ONE, 2014Co-Authors: Jia Guo, Xuan Zhang, Zhi Chen, Ying WenAbstract:Streptomyces avermitilis is an important bacterial species used for industrial production of Avermectins, a family of broad-spectrum anthelmintic agents. We previously identified the protein SAV576, a TetR family transcriptional regulator (TFR), as a downregulator of Avermectin biosynthesis that acts by controlling transcription of its major target gene SAV575 (which encodes cytochrome P450/NADPH-ferrihemoprotein reductase) and ave genes. SAV577, another TFR gene, encodes a SAV577 protein that displays high amino acid homology with SAV576. In this study, we examined the effect of SAV577 on Avermectin production and the relationships between SAV576 and SAV577. SAV577 downregulated Avermectin biosynthesis indirectly, similarly to SAV576. SAV576 and SAV577 both directly repressed SAV575 transcription, and reciprocally repressed each other's expression. SAV575 transcription levels in various S. avermitilis strains were correlated with Avermectin production levels. DNase I footprinting and electrophoretic mobility shift assays indicated that SAV576 and SAV577 compete for the same binding regions, and that DNA-binding affinity of SAV576 is much stronger than that of SAV577. GST pull-down assays revealed no direct interaction between the two proteins. Taken together, these findings suggest that SAV577 regulates Avermectin production in S. avermitilis by a mechanism similar to that of SAV576, and that the role of SAV576 is dominant over that of SAV577. This is the first report of two adjacent and similar TFR genes that co-regulate antibiotic production in Streptomyces.
Jia Guo - One of the best experts on this subject based on the ideXlab platform.
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increasing Avermectin production in streptomyces avermitilis by manipulating the expression of a novel tetr family regulator and its target gene product
Applied and Environmental Microbiology, 2015Co-Authors: Wenshuai Liu, Zhi Chen, Jia Guo, Qinling Zhang, Ying WenAbstract:ABSTRACT Avermectins produced by Streptomyces avermitilis are commercially important anthelmintic agents. The detailed regulatory mechanisms of Avermectin biosynthesis remain unclear. Here, we identified SAV3619, a TetR-family transcriptional regulator designated AveT, to be an activator for both Avermectin production and morphological differentiation in S. avermitilis. AveT was shown to indirectly stimulate Avermectin production by affecting transcription of the cluster-situated activator gene aveR . AveT directly repressed transcription of its own gene ( aveT ), adjacent gene pepD2 ( sav_3620 ), sav_7490 (designated aveM ), and sav_7491 by binding to an 18-bp perfect palindromic sequence (CGAAACGKTKYCGTTTCG, where K is T or G and Y is T or C and where the underlining indicates inverted repeats) within their promoter regions. aveM (which encodes a putative transmembrane efflux protein belonging to the major facilitator superfamily [MFS]), the important target gene of AveT, had a striking negative effect on Avermectin production and morphological differentiation. Overexpression of aveT and deletion of aveM in wild-type and industrial strains of S. avermitilis led to clear increases in the levels of Avermectin production. In vitro gel-shift assays suggested that C-5–O-B1, the late pathway precursor of Avermectin B1, acts as an AveT ligand. Taken together, our findings indicate positive-feedback regulation of aveT expression and Avermectin production by a late pathway intermediate and provide the basis for an efficient strategy to increase Avermectin production in S. avermitilis by manipulation of AveT and its target gene product, AveM.
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two adjacent and similar tetr family transcriptional regulator genes sav577 and sav576 co regulate Avermectin production in streptomyces avermitilis
PLOS ONE, 2014Co-Authors: Jia Guo, Xuan Zhang, Zhi Chen, Ying WenAbstract:Streptomyces avermitilis is an important bacterial species used for industrial production of Avermectins, a family of broad-spectrum anthelmintic agents. We previously identified the protein SAV576, a TetR family transcriptional regulator (TFR), as a downregulator of Avermectin biosynthesis that acts by controlling transcription of its major target gene SAV575 (which encodes cytochrome P450/NADPH-ferrihemoprotein reductase) and ave genes. SAV577, another TFR gene, encodes a SAV577 protein that displays high amino acid homology with SAV576. In this study, we examined the effect of SAV577 on Avermectin production and the relationships between SAV576 and SAV577. SAV577 downregulated Avermectin biosynthesis indirectly, similarly to SAV576. SAV576 and SAV577 both directly repressed SAV575 transcription, and reciprocally repressed each other's expression. SAV575 transcription levels in various S. avermitilis strains were correlated with Avermectin production levels. DNase I footprinting and electrophoretic mobility shift assays indicated that SAV576 and SAV577 compete for the same binding regions, and that DNA-binding affinity of SAV576 is much stronger than that of SAV577. GST pull-down assays revealed no direct interaction between the two proteins. Taken together, these findings suggest that SAV577 regulates Avermectin production in S. avermitilis by a mechanism similar to that of SAV576, and that the role of SAV576 is dominant over that of SAV577. This is the first report of two adjacent and similar TFR genes that co-regulate antibiotic production in Streptomyces.
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a novel tetr family transcriptional regulator sav576 negatively controls Avermectin biosynthesis in streptomyces avermitilis
PLOS ONE, 2013Co-Authors: Jia Guo, Xuan Zhang, Shuai Luo, Zhi Chen, Ying WenAbstract:Avermectins produced by Streptomyces avermitilis are potent anti-parasitic agents that are useful in animal health care, agriculture, and the treatment of human infections. In a search for novel regulators that affect Avermectin biosynthesis, comparative transcriptome analysis was performed between wild-type strain ATCC31267 and Avermectin overproducing strain 76-02-e, revealing some differentially expressed genes. SAV576, which is downregulated in 76-02-e and encodes a TetR family transcriptional regulator (TFR), was shown to inhibit Avermectin production by indirectly affecting the expression of ave genes. SAV576 directly repressed the transcription of its gene SAV576 and of adjacent genes SAV575 (encodes cytochrome P450/NADPH-ferrihemoprotein reductase) and SAV574. The SAV576-binding sites within the bidirectional SAV575-SAV576 promoter region were determined by DNase I footprinting assays. A consensus 15-bp palindromic sequence CCRTACRVYGTATGS was found in these binding sites and shown to be important for SAV576-binding activity. SAV575, an important target gene of SAV576, was shown to exert a positive effect on Avermectin production. The study findings extend our limited knowledge of the complex regulation of Avermectin biosynthesis and provide a basis for rational genetic manipulation of S. avermitilis to improve Avermectin production through control of SAV576 and its target gene.
Xuan Zhang - One of the best experts on this subject based on the ideXlab platform.
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two adjacent and similar tetr family transcriptional regulator genes sav577 and sav576 co regulate Avermectin production in streptomyces avermitilis
PLOS ONE, 2014Co-Authors: Jia Guo, Xuan Zhang, Zhi Chen, Ying WenAbstract:Streptomyces avermitilis is an important bacterial species used for industrial production of Avermectins, a family of broad-spectrum anthelmintic agents. We previously identified the protein SAV576, a TetR family transcriptional regulator (TFR), as a downregulator of Avermectin biosynthesis that acts by controlling transcription of its major target gene SAV575 (which encodes cytochrome P450/NADPH-ferrihemoprotein reductase) and ave genes. SAV577, another TFR gene, encodes a SAV577 protein that displays high amino acid homology with SAV576. In this study, we examined the effect of SAV577 on Avermectin production and the relationships between SAV576 and SAV577. SAV577 downregulated Avermectin biosynthesis indirectly, similarly to SAV576. SAV576 and SAV577 both directly repressed SAV575 transcription, and reciprocally repressed each other's expression. SAV575 transcription levels in various S. avermitilis strains were correlated with Avermectin production levels. DNase I footprinting and electrophoretic mobility shift assays indicated that SAV576 and SAV577 compete for the same binding regions, and that DNA-binding affinity of SAV576 is much stronger than that of SAV577. GST pull-down assays revealed no direct interaction between the two proteins. Taken together, these findings suggest that SAV577 regulates Avermectin production in S. avermitilis by a mechanism similar to that of SAV576, and that the role of SAV576 is dominant over that of SAV577. This is the first report of two adjacent and similar TFR genes that co-regulate antibiotic production in Streptomyces.
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a novel tetr family transcriptional regulator sav576 negatively controls Avermectin biosynthesis in streptomyces avermitilis
PLOS ONE, 2013Co-Authors: Jia Guo, Xuan Zhang, Shuai Luo, Zhi Chen, Ying WenAbstract:Avermectins produced by Streptomyces avermitilis are potent anti-parasitic agents that are useful in animal health care, agriculture, and the treatment of human infections. In a search for novel regulators that affect Avermectin biosynthesis, comparative transcriptome analysis was performed between wild-type strain ATCC31267 and Avermectin overproducing strain 76-02-e, revealing some differentially expressed genes. SAV576, which is downregulated in 76-02-e and encodes a TetR family transcriptional regulator (TFR), was shown to inhibit Avermectin production by indirectly affecting the expression of ave genes. SAV576 directly repressed the transcription of its gene SAV576 and of adjacent genes SAV575 (encodes cytochrome P450/NADPH-ferrihemoprotein reductase) and SAV574. The SAV576-binding sites within the bidirectional SAV575-SAV576 promoter region were determined by DNase I footprinting assays. A consensus 15-bp palindromic sequence CCRTACRVYGTATGS was found in these binding sites and shown to be important for SAV576-binding activity. SAV575, an important target gene of SAV576, was shown to exert a positive effect on Avermectin production. The study findings extend our limited knowledge of the complex regulation of Avermectin biosynthesis and provide a basis for rational genetic manipulation of S. avermitilis to improve Avermectin production through control of SAV576 and its target gene.
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enhancement of Avermectin and ivermectin production by overexpression of the maltose atp binding cassette transporter in streptomyces avermitilis
Bioresource Technology, 2010Co-Authors: Zhi Chen, Xuan Zhang, Yuan Song, Ying WenAbstract:We investigated the function of maltose ABC transporter system encoded by malEFG-a and the effect of its overexpression on antibiotic production in Streptomyces avermitilis. A malEFG-a deletion mutant was unable to grow in a minimal medium with maltose as sole carbon source and produce Avermectin. Maltose utilization and Avermectin production were restored by introduction of a single copy of malEFG-a. RT-PCR analysis showed that the expression of malE-a was induced by maltose, and was strongly repressed by glucose. When multi-copy, integrative malEFG-a gene expression vectors were introduced into wild-type strain ATCC31267 and ivermectin-producer OI-31, antibiotic production increased by 2.6- to 3.3-fold and the time required for fermentation decreased by about 10%. The overexpression of malEFG-a improved the utilization rate of starch, and thereby enhanced Avermectin production. Such an approach would be useful for the improvement of commercial antibiotic production using starch as the main carbon source in the fermentation process.
Yuan Song - One of the best experts on this subject based on the ideXlab platform.
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Organic Peroxide-Sensing Repressor OhrR Regulates Organic Hydroperoxide Stress Resistance and Avermectin Production in Streptomyces avermitilis.
Frontiers in Microbiology, 2018Co-Authors: Yuan Song, Jilun Li, Zhi ChenAbstract:The bacterium Streptomyces avermitilis is an industrial-scale producer of Avermectins, which are important anthelmintic agents widely used in agriculture, veterinary medicine, and human medicine. During the Avermectin fermentation process, S. avermitilis is exposed to organic peroxides generated by aerobic respiration. We investigated the role of MarR-family transcriptional regulator OhrR in oxidative stress response and Avermectin production in S. avermitilis. The S. avermitilis genome encodes two organic hydroperoxide resistance proteins: OhrB1 and OhrB2. OhrB2 is the major resistance protein in organic peroxide stress responses. In the absence of organic peroxide, the reduced form of OhrR represses the expression of ohrB2 gene by binding to the OhrR box in the promoter region. In the presence of organic peroxide, the oxidized form of OhrR dissociates from the OhrR box and the expression of ohrB2 is increased by derepression. OhrR also acts as a repressor to regulate its own expression. An ohrR-deletion mutant (termed DohrR) displayed enhanced Avermectin production. Our findings demonstrate that OhrR in S. avermitilis represses Avermectin production by regulating the expression of pathway-specific regulatory gene aveR. OhrR also plays a regulatory role in glycolysis and the pentose phosphate (PP) pathway by negatively controlling the expression of pykA2 and ctaB/tkt2-tal2-zwf2-opcA2-pgl.
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Data_Sheet_1_Organic Peroxide-Sensing Repressor OhrR Regulates Organic Hydroperoxide Stress Resistance and Avermectin Production in Streptomyces avermitilis.PDF
2018Co-Authors: Meng Sun, Ying Wen, Yuan Song, Mengya Lyu, Zhi ChenAbstract:The bacterium Streptomyces avermitilis is an industrial-scale producer of Avermectins, which are important anthelmintic agents widely used in agriculture, veterinary medicine, and human medicine. During the Avermectin fermentation process, S. avermitilis is exposed to organic peroxides generated by aerobic respiration. We investigated the role of MarR-family transcriptional regulator OhrR in oxidative stress response and Avermectin production in S. avermitilis. The S. avermitilis genome encodes two organic hydroperoxide resistance proteins: OhrB1 and OhrB2. OhrB2 is the major resistance protein in organic peroxide stress responses. In the absence of organic peroxide, the reduced form of OhrR represses the expression of ohrB2 gene by binding to the OhrR box in the promoter region. In the presence of organic peroxide, the oxidized form of OhrR dissociates from the OhrR box and the expression of ohrB2 is increased by derepression. OhrR also acts as a repressor to regulate its own expression. An ohrR-deletion mutant (termed DohrR) displayed enhanced Avermectin production. Our findings demonstrate that OhrR in S. avermitilis represses Avermectin production by regulating the expression of pathway-specific regulatory gene aveR. OhrR also plays a regulatory role in glycolysis and the pentose phosphate (PP) pathway by negatively controlling the expression of pykA2 and ctaB/tkt2-tal2-zwf2-opcA2-pgl.
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enhancement of Avermectin and ivermectin production by overexpression of the maltose atp binding cassette transporter in streptomyces avermitilis
Bioresource Technology, 2010Co-Authors: Zhi Chen, Xuan Zhang, Yuan Song, Ying WenAbstract:We investigated the function of maltose ABC transporter system encoded by malEFG-a and the effect of its overexpression on antibiotic production in Streptomyces avermitilis. A malEFG-a deletion mutant was unable to grow in a minimal medium with maltose as sole carbon source and produce Avermectin. Maltose utilization and Avermectin production were restored by introduction of a single copy of malEFG-a. RT-PCR analysis showed that the expression of malE-a was induced by maltose, and was strongly repressed by glucose. When multi-copy, integrative malEFG-a gene expression vectors were introduced into wild-type strain ATCC31267 and ivermectin-producer OI-31, antibiotic production increased by 2.6- to 3.3-fold and the time required for fermentation decreased by about 10%. The overexpression of malEFG-a improved the utilization rate of starch, and thereby enhanced Avermectin production. Such an approach would be useful for the improvement of commercial antibiotic production using starch as the main carbon source in the fermentation process.
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Selection of high Avermectins producing strain and identification of Avermectin B1
Sheng wu gong cheng xue bao = Chinese journal of biotechnology, 2000Co-Authors: Yuan Song, Zhangliang ChenAbstract:Three types of colony, powdery gray, white and bald, were isolated from Streptomyces avermitilis ATCC31272. Among them, only the powdery grey one produces Avermectins. Sa-76 strain was selected from the powdery grey strain by mutation with high energy electric flow, and its Avermectins titer attainde 100 micrograms/mL in shaking flask. Avermectin B1 was extracted and purified from the mycelia of Sa-76, and identified by UV, IR, 1H-NMR, 13C-NMR and mass spectra. After Sa-76 strain was treated twice with NTG, a strain named Sa-76-8 was selected with Avermectins titer over 2000 micrograms/mL. The Sa-76-8 strain was treated with NTG once again, and a high Avermectins producing strain named as Sa-76-9 with Avermectins titer up to 3500-4000 micrograms/mL was selected.
