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Guang-rong Zhao - One of the best experts on this subject based on the ideXlab platform.
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comparative transcriptomic analysis reveals the significant pleiotropic regulatory effects of lmbu on Lincomycin biosynthesis
Microbial Cell Factories, 2020Co-Authors: Chun-yan Lin, Jianjun Qiao, Aiping Pang, Yue Zhang, Guang-rong ZhaoAbstract:Lincomycin, produced by Streptomyces lincolnensis, is a lincosamide antibiotic and widely used for the treatment of the infective diseases caused by Gram-positive bacteria. The mechanisms of Lincomycin biosynthesis have been deeply explored in recent years. However, the regulatory effects of LmbU that is a transcriptional regulator in Lincomycin biosynthetic (lmb) gene cluster have not been fully addressed. LmbU was used to search for homologous LmbU (LmbU-like) proteins in the genomes of actinobacteria, and the results showed that LmbU-like proteins are highly distributed regulators in the biosynthetic gene clusters (BGCs) of secondary metabolites or/and out of the BGCs in actinomycetes. The overexpression, inactivation and complementation of the lmbU gene indicated that LmbU positively controls Lincomycin biosynthesis in S. lincolnensis. Comparative transcriptomic analysis further revealed that LmbU activates the 28 lmb genes at whole lmb cluster manner. Furthermore, LmbU represses the transcription of the non-lmb gene hpdA in the biosynthesis of l-tyrosine, the precursor of Lincomycin. LmbU up-regulates nineteen non-lmb genes, which would be involved in multi-drug flux to self-resistance, nitrate and sugar transmembrane transport and utilization, and redox metabolisms. LmbU is a significant pleiotropic transcriptional regulator in Lincomycin biosynthesis by entirely activating the lmb cluster and regulating the non-lmb genes in Streptomyces lincolnensis. Our results first revealed the pleiotropic regulatory function of LmbU, and shed new light on the transcriptional effects of LmbU-like family proteins on antibiotic biosynthesis in actinomycetes.
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Co-overexpression of lmbW and metK led to increased Lincomycin A production and decreased byproduct Lincomycin B content in an industrial strain of Streptomyces lincolnensis
Journal of applied microbiology, 2015Co-Authors: A.‐p. Pang, Chun-yan Lin, Jianjun Qiao, Guang-rong ZhaoAbstract:Aims To improve Lincomycin A production and decrease the content of byproduct Lincomycin B in an industrial Lincomycin-producing strain. Methods and Results The in silico analysis indicated that LmbW could be involved in propylproline biosynthesis of lincomyin A. In this study, we constructed an lmbW deletion mutant and found that the mutant lost the ability to produce Lincomycin A, but increased the accumulation of Lincomycin B. The loss of Lincomycin A production can be restored by complementing the mutant with the expression of lmbW gene. When lmbW and metK (encoding S-adenosylmethionine synthetase) was co-overexpressed, Lincomycin A titre was 1744·6 mg l−1, a 35·83% improvement over the original strain. Meanwhile, the content of Lincomycin B was reduced to 4·41%, a remarkable decrease of 34·76%, compared to that of the original strain. Conclusions lmbW encodes a C-methyltransferase involved in the biosynthesis of Lincomycin A but not Lincomycin B. Co-overexpression of lmbW and metK improved Lincomycin A production and decreased the content of Lincomycin B. Significance and Impact of the Study The engineered Streptomyces lincolnensis strain shows promising application in the fermentation production of Lincomycin A, which may help cut production costs and simplify downstream separation processes.
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Improved industrial fermentation of Lincomycin by phosphorus feeding
Process Biochemistry, 2007Co-Authors: Xiao-bing Li, Guang-rong Zhao, Hui Zheng, Ying-jin YuanAbstract:Abstract Phosphorus limitation was found in the fermentation production of Lincomycin based on the phosphorus elemental analysis. Phosphorus was thus fed into the fermentation system to improve the Lincomycin production, and 16 kg fed-phosphorus increased the Lincomycin yield by 14.4% compared to that without the phosphorus feeding. As low concentration of dissolved oxygen limited the growth of mycelia, the phosphorus in the base medium and fed-batch were adjusted to give a more reasonable phosphorus distribution. When the phosphorus in the base medium was decreased to 29.4 kg from 33.4 kg and the fed phosphorus was increased from 16.0 kg to 20.0 kg in a 100 m3 fermenter, the final Lincomycin titer increased by 21.6% compared to that the un-fed process. The mycelia growth and Lincomycin production rates were also increased at the production stage. The phosphorus feeding and adjustment distribution strategy might be applied to other industrial fermentation processes to improve the process efficiency and productivity.
Huiling Liu - One of the best experts on this subject based on the ideXlab platform.
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Dosage effects of Lincomycin mycelial residues on Lincomycin resistance genes and soil microbial communities.
Environmental pollution (Barking Essex : 1987), 2019Co-Authors: Mengmeng Wang, Huiling Liu, Xiaohu DaiAbstract:Abstract Lincomycin mycelial residues (LMRs) are one kind of byproduct of the pharmaceutical industry. Hydrothermal treatment has been used to dispose of them and land application is an attractive way to reuse the treated LMRs. However, the safe dose for soil amendment remains unclear. In this study, a lab-scale incubation experiment was conducted to investigate the influence of the amendment dosage on Lincomycin resistance genes and soil bacterial communities via quantitative PCR and 16S rRNA sequencing. The results showed that introduced Lincomycin degraded quickly in soil and became undetectable after 50 days. Degradation rate of the high amendment amount (100 mg kg−1) was almost 4 times faster than that of low amendment amount (10 mg kg−1). Moreover, the introduced LMRs induced the increase of Lincomycin resistance genes after incubation for 8 days, and two genes (lmrA and lnuB) showed a dosage-related increase. For example, the abundance of gene lmrA was 17.78, 74.13 and 128.82 copies g−1 soil for Lincomycin concentration of 10, 50 and 100 mg kg−1, respectively. However, the abundance of Lincomycin resistance genes recovered to the control level as the incubation period extended to 50 days, indicating a low persistence in soil. In addition, LMRs application markedly shifted the bacterial composition and significant difference was found between control soil, 10 mg kg−1 and 50 mg kg−1 Lincomycin amended soil. Actually, several genera bacteria were significantly related to the elevation of Lincomycin resistance genes. These results provided a comprehensive understanding of the effects of Lincomycin dosage on the fate of resistance genes and microbial communities in LMRs applied soil.
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degradation of Lincomycin in aqueous solution with hydrothermal treatment kinetics pathway and toxicity evaluation
Chemical Engineering Journal, 2018Co-Authors: Mengmeng Wang, Chen Cai, Bo Zhang, Yanjun Xin, Jing Wang, Huiling LiuAbstract:Abstract Recently, Lincomycin has been detected frequently in aquatic environment, especially in the effluent of pharmaceutical wastewater treatment plants. Public concerns have been raised due to its adverse bio-effect and potential of inducing resistance genes. In this study, hydrothermal treatment (HT) was applied to remove Lincomycin from high-concentrated pharmaceutical waste water. Influence factors (e.g., temperature, initial concentration and pH) were investigated from kinetics perspective. Meanwhile, degradation byproducts were identified using liquid chromatography–mass spectrometry (LC–MS), based on that transformation pathways were proposed. Finally, the toxicity of Lincomycin degradation intermediates were evaluated by Microcystis cells. The results showed that Lincomycin was eliminated efficiently via HT and an obvious lag time existed in its degradation process. An autocatalytic model was developed successfully based on the degradation kinetics analysis. The model showed good fitness with experiments data (R2 > 0.99). Observed reaction constant (k) increased when reaction temperature varied from 110 to 160 °C; it decreased from 0.034 to 0.015 min−1 as pH ranged from 2.0 to 6.0. Additionally, increasing initial concentration of Lincomycin promoted its degradation, while it showed a different trend once the concentration exceeded 300 mg L−1. A total of 7 major intermediates were identified, based on which hydrolysis, hydroxylation and desulfuration were inferred as the mainly evolution processes. Finally, toxicity evaluation indicated that both Lincomycin and its degradation byproducts have no inhibition on algal strains. Thus, it is concluded that HT is an efficient method for removing Lincomycin.
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Acidic hydrothermal treatment: Characteristics of organic, nitrogen and phosphorus releasing and process optimization on Lincomycin removal from Lincomycin mycelial residues
Chemical Engineering Journal, 2018Co-Authors: Mengmeng Wang, Chen Cai, Bo Zhang, Yanjun Xin, Huiling LiuAbstract:Abstract Lincomycin mycelial residues (LMRs), one kind of bio-wastes with a high biomass organic content, are limited to use due to residual Lincomycin. Recycling of LMRs is not only benefit to economy but also to environment. This study developed an acidic hydrothermal method for LMRs treatment. Effects of reaction temperature (100, 130 and 160 °C), residence time (60, 120 and 180 min), and H2SO4 concentration (0.2, 0.4 and 0.6 M) on the amount and distributions of organics, nitrogen and phosphorus were investigated. In addition, these three crucial parameters for maximum removal of Lincomycin were optimized using response surface methodology (RSM). Meanwhile, intermediates of Lincomycin treated by acidic hydrothermal treatment (AHT) were identified by liquid chromatography – mass spectrometry (LC/MS). Antibacterial assessments of them were conducted via disk diffusion tests. Results showed that the treatments led to 34.7%–251% and 30.9%–214% in the concentrations of TN and TP, respectively, and 1.44–3.89 times higher of SCOD in the soluble phase of LMRs. Lincomycin removal rates increased with the increasing of reaction temperature, residence time and H2SO4 concentration in a certain range. The optimal conditions were obtained at activation temperature of 160 °C, residence time of 157.2 min and a H2SO4 concentration of 0.53 M, where 98.3% of Lincomycin was removed. Moreover, inhibition of Lincomycin after AHT on Staphyococcus aureus, with respect to untreated solutions containing this compound reduced significantly. Therefore, recycling of LMRs is promising after removal residual Lincomycin via AHT.
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Characterization and mechanism analysis of Lincomycin biodegradation with Clostridium sp. strain LCM-B isolated from Lincomycin mycelial residue (LMR).
Chemosphere, 2017Co-Authors: Mengmeng Wang, Chen Cai, Bo Zhang, Huiling LiuAbstract:Abstract Lincomycin mycelial residue (LMR) is the restricted resource because it contains residual Lincomycin, which is producing potential risks to the environment and human health. In this study, Lincomycin-degrading strain LCM-B was isolated and identified as Clostridium sp. in the LMR. Strain LCM-B was able to degrade 62.03% of Lincomycin at the initial concentration of 100 mg L−1 after incubation for 10 d, while only 15.61% of Lincomycin was removed at the initial concentration of 500 mg L−1. The removal efficiency of Lincomycin by strain LCM-B decreased as the initial concentration increased. Gene lnuB (which encodes the nucleotidyl transferase) was detected in the isolated strain, and it was proven to participate in Lincomycin biodegradation based on the analysis of degradation products and pathway. The results provide a relatively complete understanding of Lincomycin biodegradation mechanism. Strain LCM-B is promising to eliminate Lincomycin from the LMR.
Mengmeng Wang - One of the best experts on this subject based on the ideXlab platform.
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Dosage effects of Lincomycin mycelial residues on Lincomycin resistance genes and soil microbial communities.
Environmental pollution (Barking Essex : 1987), 2019Co-Authors: Mengmeng Wang, Huiling Liu, Xiaohu DaiAbstract:Abstract Lincomycin mycelial residues (LMRs) are one kind of byproduct of the pharmaceutical industry. Hydrothermal treatment has been used to dispose of them and land application is an attractive way to reuse the treated LMRs. However, the safe dose for soil amendment remains unclear. In this study, a lab-scale incubation experiment was conducted to investigate the influence of the amendment dosage on Lincomycin resistance genes and soil bacterial communities via quantitative PCR and 16S rRNA sequencing. The results showed that introduced Lincomycin degraded quickly in soil and became undetectable after 50 days. Degradation rate of the high amendment amount (100 mg kg−1) was almost 4 times faster than that of low amendment amount (10 mg kg−1). Moreover, the introduced LMRs induced the increase of Lincomycin resistance genes after incubation for 8 days, and two genes (lmrA and lnuB) showed a dosage-related increase. For example, the abundance of gene lmrA was 17.78, 74.13 and 128.82 copies g−1 soil for Lincomycin concentration of 10, 50 and 100 mg kg−1, respectively. However, the abundance of Lincomycin resistance genes recovered to the control level as the incubation period extended to 50 days, indicating a low persistence in soil. In addition, LMRs application markedly shifted the bacterial composition and significant difference was found between control soil, 10 mg kg−1 and 50 mg kg−1 Lincomycin amended soil. Actually, several genera bacteria were significantly related to the elevation of Lincomycin resistance genes. These results provided a comprehensive understanding of the effects of Lincomycin dosage on the fate of resistance genes and microbial communities in LMRs applied soil.
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degradation of Lincomycin in aqueous solution with hydrothermal treatment kinetics pathway and toxicity evaluation
Chemical Engineering Journal, 2018Co-Authors: Mengmeng Wang, Chen Cai, Bo Zhang, Yanjun Xin, Jing Wang, Huiling LiuAbstract:Abstract Recently, Lincomycin has been detected frequently in aquatic environment, especially in the effluent of pharmaceutical wastewater treatment plants. Public concerns have been raised due to its adverse bio-effect and potential of inducing resistance genes. In this study, hydrothermal treatment (HT) was applied to remove Lincomycin from high-concentrated pharmaceutical waste water. Influence factors (e.g., temperature, initial concentration and pH) were investigated from kinetics perspective. Meanwhile, degradation byproducts were identified using liquid chromatography–mass spectrometry (LC–MS), based on that transformation pathways were proposed. Finally, the toxicity of Lincomycin degradation intermediates were evaluated by Microcystis cells. The results showed that Lincomycin was eliminated efficiently via HT and an obvious lag time existed in its degradation process. An autocatalytic model was developed successfully based on the degradation kinetics analysis. The model showed good fitness with experiments data (R2 > 0.99). Observed reaction constant (k) increased when reaction temperature varied from 110 to 160 °C; it decreased from 0.034 to 0.015 min−1 as pH ranged from 2.0 to 6.0. Additionally, increasing initial concentration of Lincomycin promoted its degradation, while it showed a different trend once the concentration exceeded 300 mg L−1. A total of 7 major intermediates were identified, based on which hydrolysis, hydroxylation and desulfuration were inferred as the mainly evolution processes. Finally, toxicity evaluation indicated that both Lincomycin and its degradation byproducts have no inhibition on algal strains. Thus, it is concluded that HT is an efficient method for removing Lincomycin.
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Acidic hydrothermal treatment: Characteristics of organic, nitrogen and phosphorus releasing and process optimization on Lincomycin removal from Lincomycin mycelial residues
Chemical Engineering Journal, 2018Co-Authors: Mengmeng Wang, Chen Cai, Bo Zhang, Yanjun Xin, Huiling LiuAbstract:Abstract Lincomycin mycelial residues (LMRs), one kind of bio-wastes with a high biomass organic content, are limited to use due to residual Lincomycin. Recycling of LMRs is not only benefit to economy but also to environment. This study developed an acidic hydrothermal method for LMRs treatment. Effects of reaction temperature (100, 130 and 160 °C), residence time (60, 120 and 180 min), and H2SO4 concentration (0.2, 0.4 and 0.6 M) on the amount and distributions of organics, nitrogen and phosphorus were investigated. In addition, these three crucial parameters for maximum removal of Lincomycin were optimized using response surface methodology (RSM). Meanwhile, intermediates of Lincomycin treated by acidic hydrothermal treatment (AHT) were identified by liquid chromatography – mass spectrometry (LC/MS). Antibacterial assessments of them were conducted via disk diffusion tests. Results showed that the treatments led to 34.7%–251% and 30.9%–214% in the concentrations of TN and TP, respectively, and 1.44–3.89 times higher of SCOD in the soluble phase of LMRs. Lincomycin removal rates increased with the increasing of reaction temperature, residence time and H2SO4 concentration in a certain range. The optimal conditions were obtained at activation temperature of 160 °C, residence time of 157.2 min and a H2SO4 concentration of 0.53 M, where 98.3% of Lincomycin was removed. Moreover, inhibition of Lincomycin after AHT on Staphyococcus aureus, with respect to untreated solutions containing this compound reduced significantly. Therefore, recycling of LMRs is promising after removal residual Lincomycin via AHT.
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Characterization and mechanism analysis of Lincomycin biodegradation with Clostridium sp. strain LCM-B isolated from Lincomycin mycelial residue (LMR).
Chemosphere, 2017Co-Authors: Mengmeng Wang, Chen Cai, Bo Zhang, Huiling LiuAbstract:Abstract Lincomycin mycelial residue (LMR) is the restricted resource because it contains residual Lincomycin, which is producing potential risks to the environment and human health. In this study, Lincomycin-degrading strain LCM-B was isolated and identified as Clostridium sp. in the LMR. Strain LCM-B was able to degrade 62.03% of Lincomycin at the initial concentration of 100 mg L−1 after incubation for 10 d, while only 15.61% of Lincomycin was removed at the initial concentration of 500 mg L−1. The removal efficiency of Lincomycin by strain LCM-B decreased as the initial concentration increased. Gene lnuB (which encodes the nucleotidyl transferase) was detected in the isolated strain, and it was proven to participate in Lincomycin biodegradation based on the analysis of degradation products and pathway. The results provide a relatively complete understanding of Lincomycin biodegradation mechanism. Strain LCM-B is promising to eliminate Lincomycin from the LMR.
Yaqian Tang - One of the best experts on this subject based on the ideXlab platform.
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Developmental regulator BldD directly regulates Lincomycin biosynthesis in Streptomyces lincolnensis
Biochemical and biophysical research communications, 2019Co-Authors: Nian Wang, Yaqian Tang, Xinlu Cai, Ruihua Liu, Zhang BuchangAbstract:Abstract The regulatory mechanism of Lincomycin biosynthesis remains largely unknown, although Lincomycin and its derivatives have been of great application in pharmaceutical industry. As a global regulator, BldD is widespread in Streptomyces, and functions as an on-off switch to regulate the transition from morphological differentiation to secondary metabolism, inspiring us to explore scarcely regulatory realm of Lincomycin biosynthesis. In this work, deletion of bldD gene (SLCG_1664) in Streptomyces lincolnensis blocked the sporulation and nearly abolished Lincomycin production, while the morphological phenotype and Lincomycin production were restored when introducing a functional bldD gene into the ΔbldD mutant. S. lincolnensis BldD (BldDSL) was validated to bind to upstream regions of Lincomycin biosynthetic structural genes lmbA, lmbC-lmbD, lmbE, lmbV-lmbW, resistant genes lmrA, lmrB, lmrC, and regulatory gene lmbU. Disruption of bldD significantly decreased the transcription of genes in Lincomycin biosynthetic cluster, thus resulting in the sharply loss of Lincomycin production. These findings indicate that BldDSL, similar to Saccharopolyspora erythraea BldD (BldDSE), directly regulates the biosynthesis of Lincomycin. What's more, we discovered that BldDSE could bind to upstream regions of lmbA, lmbV-lmbW, lmrA and lmrC. Corresponding to this, S. lincolnensis BldD can bind to upstream region of eryAI-eryBIV, revealing an interactional regulation of the two BldDs. In summary, our data indicated that the developmental regulator BldD played a vital role in directly regulating the biosynthesis of Lincomycin, and expanded the knowledge on Lincomycin biosynthetic regulation in S. lincolnensis.
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tetr type regulator slcg_2919 is a negative regulator of Lincomycin biosynthesis in streptomyces lincolnensis
Applied and Environmental Microbiology, 2018Co-Authors: Yaqian Tang, Nian Wang, Ruihua Liu, Guoqing Tan, Yansheng Wang, Linquan Bai, Lixin Zhang, Buchang ZhangAbstract:Lincomycin A (Lin-A) is a widely used antibacterial antibiotic fermented by Streptomyces lincolnensis However, the transcriptional regulatory mechanisms underlying Lincomycin biosynthesis have seldom been investigated. Here, we first identified a TetR family transcriptional regulator (TFR), SLCG_2919, which negatively modulates Lincomycin biosynthesis in S. lincolnensis LCGL. SLCG_2919 was found to specifically bind to promoter regions of the Lincomycin biosynthetic gene cluster (lin cluster), including 25 structural genes, three resistance genes, and one regulatory gene, and to inhibit the transcription of these genes, demonstrating a directly regulatory role in Lincomycin biosynthesis. Furthermore, we found that SLCG_2919 was not autoregulated, but directly repressed its adjacent gene, SLCG_2920, which encodes an ATP/GTP binding protein whose overexpression increased resistance against Lincomycin and Lin-A yields in S. lincolnensis The precise SLCG_2919 binding site within the promoter region of SLCG_2920 was determined by a DNase I footprinting assay and by electrophoretic mobility shift assays (EMSAs) based on base substitution mutagenesis, with the internal 10-nucleotide (nt) AT-rich sequence (AAATTATTTA) shown to be essential for SLCG_2919 binding. Our findings indicate that SLCG_2919 is a negative regulator for controlling Lincomycin biosynthesis in S. lincolnensis The present study improves our understanding of molecular regulation for Lincomycin biosynthesis.IMPORTANCE TetR family transcriptional regulators (TFRs) are generally found to regulate diverse cellular processes in bacteria, especially antibiotic biosynthesis in Streptomyces species. However, knowledge of their function in Lincomycin biosynthesis in S. lincolnensis remains unknown. The present study provides a new insight into the regulation of Lincomycin biosynthesis through a TFR, SLCG_2919, that directly modulates Lincomycin production and resistance. Intriguingly, SLCG_2919 and its adjoining gene, SLCG_2920, which encodes an ATP/GTP binding protein, were extensively distributed in diverse Streptomyces species. In addition, we revealed a new TFR binding motif, in which SLCG_2919 binds to the promoter region of SLCG_2920, dependent on the intervening AT-rich sequence rather than on the flanking inverted repeats found in the binding sites of other TFRs. These insights into transcriptional regulation of Lincomycin biosynthesis by SLCG_2919 will be valuable in paving the way for genetic engineering of regulatory elements in Streptomyces species to improve antibiotic production.
Nian Wang - One of the best experts on this subject based on the ideXlab platform.
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Developmental regulator BldD directly regulates Lincomycin biosynthesis in Streptomyces lincolnensis
Biochemical and biophysical research communications, 2019Co-Authors: Nian Wang, Yaqian Tang, Xinlu Cai, Ruihua Liu, Zhang BuchangAbstract:Abstract The regulatory mechanism of Lincomycin biosynthesis remains largely unknown, although Lincomycin and its derivatives have been of great application in pharmaceutical industry. As a global regulator, BldD is widespread in Streptomyces, and functions as an on-off switch to regulate the transition from morphological differentiation to secondary metabolism, inspiring us to explore scarcely regulatory realm of Lincomycin biosynthesis. In this work, deletion of bldD gene (SLCG_1664) in Streptomyces lincolnensis blocked the sporulation and nearly abolished Lincomycin production, while the morphological phenotype and Lincomycin production were restored when introducing a functional bldD gene into the ΔbldD mutant. S. lincolnensis BldD (BldDSL) was validated to bind to upstream regions of Lincomycin biosynthetic structural genes lmbA, lmbC-lmbD, lmbE, lmbV-lmbW, resistant genes lmrA, lmrB, lmrC, and regulatory gene lmbU. Disruption of bldD significantly decreased the transcription of genes in Lincomycin biosynthetic cluster, thus resulting in the sharply loss of Lincomycin production. These findings indicate that BldDSL, similar to Saccharopolyspora erythraea BldD (BldDSE), directly regulates the biosynthesis of Lincomycin. What's more, we discovered that BldDSE could bind to upstream regions of lmbA, lmbV-lmbW, lmrA and lmrC. Corresponding to this, S. lincolnensis BldD can bind to upstream region of eryAI-eryBIV, revealing an interactional regulation of the two BldDs. In summary, our data indicated that the developmental regulator BldD played a vital role in directly regulating the biosynthesis of Lincomycin, and expanded the knowledge on Lincomycin biosynthetic regulation in S. lincolnensis.
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tetr type regulator slcg_2919 is a negative regulator of Lincomycin biosynthesis in streptomyces lincolnensis
Applied and Environmental Microbiology, 2018Co-Authors: Yaqian Tang, Nian Wang, Ruihua Liu, Guoqing Tan, Yansheng Wang, Linquan Bai, Lixin Zhang, Buchang ZhangAbstract:Lincomycin A (Lin-A) is a widely used antibacterial antibiotic fermented by Streptomyces lincolnensis However, the transcriptional regulatory mechanisms underlying Lincomycin biosynthesis have seldom been investigated. Here, we first identified a TetR family transcriptional regulator (TFR), SLCG_2919, which negatively modulates Lincomycin biosynthesis in S. lincolnensis LCGL. SLCG_2919 was found to specifically bind to promoter regions of the Lincomycin biosynthetic gene cluster (lin cluster), including 25 structural genes, three resistance genes, and one regulatory gene, and to inhibit the transcription of these genes, demonstrating a directly regulatory role in Lincomycin biosynthesis. Furthermore, we found that SLCG_2919 was not autoregulated, but directly repressed its adjacent gene, SLCG_2920, which encodes an ATP/GTP binding protein whose overexpression increased resistance against Lincomycin and Lin-A yields in S. lincolnensis The precise SLCG_2919 binding site within the promoter region of SLCG_2920 was determined by a DNase I footprinting assay and by electrophoretic mobility shift assays (EMSAs) based on base substitution mutagenesis, with the internal 10-nucleotide (nt) AT-rich sequence (AAATTATTTA) shown to be essential for SLCG_2919 binding. Our findings indicate that SLCG_2919 is a negative regulator for controlling Lincomycin biosynthesis in S. lincolnensis The present study improves our understanding of molecular regulation for Lincomycin biosynthesis.IMPORTANCE TetR family transcriptional regulators (TFRs) are generally found to regulate diverse cellular processes in bacteria, especially antibiotic biosynthesis in Streptomyces species. However, knowledge of their function in Lincomycin biosynthesis in S. lincolnensis remains unknown. The present study provides a new insight into the regulation of Lincomycin biosynthesis through a TFR, SLCG_2919, that directly modulates Lincomycin production and resistance. Intriguingly, SLCG_2919 and its adjoining gene, SLCG_2920, which encodes an ATP/GTP binding protein, were extensively distributed in diverse Streptomyces species. In addition, we revealed a new TFR binding motif, in which SLCG_2919 binds to the promoter region of SLCG_2920, dependent on the intervening AT-rich sequence rather than on the flanking inverted repeats found in the binding sites of other TFRs. These insights into transcriptional regulation of Lincomycin biosynthesis by SLCG_2919 will be valuable in paving the way for genetic engineering of regulatory elements in Streptomyces species to improve antibiotic production.