The Experts below are selected from a list of 43758 Experts worldwide ranked by ideXlab platform
Jian Chen - One of the best experts on this subject based on the ideXlab platform.
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reconstruction and analysis of the Industrial Strain bacillus megaterium wsh002 genome scale in silico metabolic model
Journal of Biotechnology, 2013Co-Authors: Wei Zou, Liming Liu, Maoda Zhou, Jian ChenAbstract:A genome-scale metabolic model of Bacillus megaterium WSH002, an Industrial bacterium widely used in the vitamin C industry, was reconstructed on the basis of the genome annotation and data from the literature and biochemical databases. It comprises 1112 reactions, 993 metabolites, and 1055 genes, including 43 new annotated genes. This model was able to predict qualitatively and quantitatively the growth of B. megaterium on a range of carbon and nitrogen sources, and the results agreed well with experimental data. A gene essentiality analysis predicted a core metabolic essential gene set of 57 genes on three different media. Furthermore, conStraint-based analysis revealed that B. megaterium WSH002 is capable of producing and exporting several key metabolites, which could promote the growth of Ketogulonicigenium vulgare and 2-keto-l-gulonic acid (2-KLG) production. Here, the model represents a helpful tool for understanding and exploring this important Industrial organism.
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reconstruction and analysis of a genome scale metabolic model of the vitamin c producing Industrial Strain ketogulonicigenium vulgare wsh 001
Journal of Biotechnology, 2012Co-Authors: Wei Zou, Liming Liu, Jing Zhang, Haoru Yang, Maoda Zhou, Qiang Hua, Jian ChenAbstract:Abstract Ketogulonicigenium vulgare WSH001 is an Industrial Strain commonly used in the vitamin C producing industry. In order to acquire a comprehensive understanding of its physiological characteristics, a genome-scale metabolic model of K. vulgare WSH001, i WZ663, including 830 reactions, 649 metabolites, and 663 genes, was reconstructed by genome annotation and literature mining. This model was capable of predicting quantitatively the growth of K. vulgare under l -sorbose fermentation conditions and the results agreed well with experimental data. Furthermore, phenotypic features, such as the defect in sulfate metabolism hampering the syntheses of l -cysteine, l -methionine, coenzyme A (CoA), and glutathione, were investigated and provided an explanation for the poor growth of K. vulgare in monoculture. The model presented here provides a validated platform that can be used to understand and manipulate the phenotype of K. vulgare to further improve 2-KLG production efficiency.
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draft genome sequence of gluconobacter oxydans wsh 003 a Strain that is extremely tolerant of saccharides and alditols
Journal of Bacteriology, 2012Co-Authors: Lili Gao, Jingwen Zhou, Jie Liu, Jian ChenAbstract:Gluconobacter oxydans is known for its incomplete oxidation of a wide range of alcohols, sugars, and acids in a bioprocess. The corresponding oxidation products are secreted almost completely into the medium. Here, we present the high-quality draft genome sequence of G. oxydans WSH-003, an Industrial Strain with both high l-sorbose productivity and extreme tolerance to saccharides and alditols.
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complete genome sequence of the Industrial Strain bacillus megaterium wsh 002
Journal of Bacteriology, 2011Co-Authors: Liming Liu, Jie Liu, Lei Wang, Jing Zhang, Wei Zou, Zhemin Zhou, Jian ChenAbstract:ABSTRACT Bacillus megaterium, an Industrial Strain, has been widely used in protein production and the vitamin C industry. Here we reported a finished, annotated, and compared 4.14-Mbp high-quality genome sequence of B. megaterium WSH-002, which is the companion Strain for Ketogulonicigenium vulgare in the vitamin C industry and is stocked in our laboratory.
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complete genome sequence of the Industrial Strain ketogulonicigenium vulgare wsh 001
Journal of Bacteriology, 2011Co-Authors: Liming Liu, Jingwen Zhou, Jie Liu, Lei Wang, Jing Zhang, Zhemin Zhou, Jian ChenAbstract:Ketogulonicigenium vulgare is an Industrial organism commonly used in the vitamin C industry. Here, we report the finished, annotated, and compared 3.28-Mbp high-quality genome sequence of Ketogulonicigenium vulgare WSH-001, a 2-keto-l-gulonic acid-producing Industrial Strain stocked in our laboratory.
Yong Yang - One of the best experts on this subject based on the ideXlab platform.
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Increased flux through the TCA cycle enhances bacitracin production by Bacillus licheniformis DW2.
Applied microbiology and biotechnology, 2018Co-Authors: Zhaoyuan Liu, Christopher T Nomura, Shouwen Chen, Yong Yang, Qin WangAbstract:The dodecapeptide antibiotic bacitracin, produced by several Strains of Bacillus licheniformis and Bacillus subtilis, is widely used as an antibacterial animal feed additive. Several genetic strategies were explored to enhance its production. The availability of building block amino acids for bacitracin production was found to play an important role in its synthesis. In this study, the TCA cycle in the Industrial Strain B. licheniformis DW2 was strengthened by overexpression of the key enzymes citrate synthase and isocitrate dehydrogenase (ICDH). As the central metabolic pathway, the TCA cycle is a major source for energy supply and intermediates for anabolism. By enhancing flux through the TCA cycle, more energy and precursors were generated for amino acid biosynthesis and uptake, resulting in enlarged intracellular pool of bacitracin-containing amino acids for bacitracin production. This study unveiled the metabolic responses of the increased TCA cycle flux in B. licheniformis and provided a novel strategy for enhancing bacitracin production.
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enhanced single step bioproduction of the simvastatin precursor monacolin j in an Industrial Strain of aspergillus terreus by employing the evolved lovastatin hydrolase
Biotechnology Journal, 2018Co-Authors: Bo Liang, Yong Yang, Xuenian Huang, Yajing Liang, Yun Teng, Linghui ZhengAbstract:Biosynthesis of simvastatin, the active pharmaceutical ingredient of cholesterol-lowering drug Zocor, has drawn increasing global attention in recent years. Although single-step in vivo production of monacolin J, the intermediate biosynthetic precursor of simvastatin, has been realized by utilizing lovastatin hydrolase (PcEST) in our previous study, about 5% of residual lovastatin is still a problem for Industrial production and quality control. In order to improve conversion efficiency and reduce lovastatin residues, modification of PcEST is carried out through directed evolution and a novel two-step high-throughput screening method. The mutant Q140L shows 18-fold improved whole-cell activity as compared to the wild-type, and one fold enhanced catalytic efficiency and 3 °C increased T5010 over the wild-type are observed by characterizing the purified protein. Finally, the engineered A. terreus Strain overexpressing Q140L mutant exhibited the increased conversion efficiency and the reduced lovastatin residues by comparing with A. terreus Strain overexpressing the wild-type PcEST, where almost 100% of the produced lovastatin is hydrolyzed to monacolin J. Therefore, this improved microbial cell factory can realize single-step bioproduction of monacolin J in a more efficient way, providing an attractive and eco-friendly substitute over the existing chemical synthetic routes of monacolin J and promoting complete bioproduction of simvastatin at Industrial scale.
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enhanced single step bioproduction of the simvastatin precursor monacolin j in an Industrial Strain of aspergillus terreus by employing the evolved lovastatin hydrolase
Biotechnology Journal, 2018Co-Authors: Bo Liang, Yong Yang, Xuenian Huang, Yajing Liang, Yun Teng, Linghui ZhengAbstract:Biosynthesis of simvastatin, the active pharmaceutical ingredient of cholesterol-lowering drug Zocor, has drawn increasing global attention in recent years. Although single-step in vivo production of monacolin J, the intermediate biosynthetic precursor of simvastatin, has been realized by utilizing lovastatin hydrolase (PcEST) in our previous study, about 5% of residual lovastatin is still a problem for Industrial production and quality control. In order to improve conversion efficiency and reduce lovastatin residues, modification of PcEST is carried out through directed evolution and a novel two-step high-throughput screening method. The mutant Q140L shows 18-fold improved whole-cell activity as compared to the wild-type, and one fold enhanced catalytic efficiency and 3 degrees C increased T-50(10) over the wild-type are observed by characterizing the purified protein. Finally, the engineered A. terreus Strain overexpressing Q140L mutant exhibited the increased conversion efficiency and the reduced lovastatin residues by comparing with A. terreus Strain overexpressing the wild-type PcEST, where almost 100% of the produced lovastatin is hydrolyzed to monacolin J. Therefore, this improved microbial cell factory can realize single-step bioproduction of monacolin J in a more efficient way, providing an attractive and eco-friendly substitute over the existing chemical synthetic routes of monacolin J and promoting complete bioproduction of simvastatin at Industrial scale.
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single step production of the simvastatin precursor monacolin j by engineering of an Industrial Strain of aspergillus terreus
Metabolic Engineering, 2017Co-Authors: Xuenian Huang, Yajing Liang, Yong YangAbstract:Monacolin J is a key precursor for the synthesis of simvastatin (Zocor), an important drug for treating hypercholesterolemia. Industrially, monacolin J is manufactured through alkaline hydrolysis of lovastatin, a fungal polyketide produced by Aspergillus terreus. Multistep chemical processes for the conversion of lovastatin to simvastatin are laborious, cost expensive and environmentally unfriendly. A biocatalysis process for monacolin J conversion to simvastatin has been developed. However, direct bioproduction of monacolin J has not yet been achieved. Here, we identified a lovastatin hydrolase from Penicillium chrysogenum, which displays a 232-fold higher catalytic efficiency for the in vitro hydrolysis of lovastatin compared to a previously patented hydrolase, but no activity for simvastatin. Furthermore, we showed that an Industrial A. terreus Strain heterologously expressing this lovastatin hydrolase can produce monacolin J through single-step fermentation with high efficiency, approximately 95% of the biosynthesized lovastatin was hydrolyzed to monacolin J. Our results demonstrate a simple and green technical route for the production of monacolin J, which makes complete bioproduction of the cholesterol-lowering drug simvastatin feasible and promising.
Linghui Zheng - One of the best experts on this subject based on the ideXlab platform.
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overproduction of gentamicin b in Industrial Strain micromonospora echinospora cctcc m 2018898 by cloning of the missing genes genr and gens
Metabolic Engineering Communications, 2019Co-Authors: Yingying Chang, Zixin Deng, Yun Teng, Linghui Zheng, Baozhong Chai, Yunkun Ding, Tiangang LiuAbstract:In pharmaceutical industry, isepamicin is mainly manufactured from gentamicin B, which is produced by Micromonospora echinospora as a minor component of the gentamicin complex. Improvement of gentamicin B production through metabolic engineering is therefore important to satisfy the increasing demand for isepamicin. We hypothesized that gentamicin B was generated from gentamicin JI-20A via deamination of the C2’ amino group. Using kanJ and kanK as the gene probes, we identified the putative deamination-related genes, genR and genS, through genome mining of the gentamicin B producing Strain M. echinospora CCTCC M 2018898. Interestingly, genR and genS constitute a gene cassette located approximately 28.7 kb away from the gentamicin gene cluster. Gene knockout of genR and genS almost abolished the production of gentamicin B in the mutant Strain, suggesting that these two genes, which are responsible for the last steps in gentamicin B biosynthesis, constitute the missing part of the known gentamicin biosynthetic pathway. Based on these finding, we successfully constructed a gentamicin B high-yielding Strain (798 mg/L), in which an overexpression cassette of genR and genS was introduced. Our work fills the missing piece to solve the puzzle of gentamicin B biosynthesis and may inspire future metabolic engineering efforts to generate gentamycin B high-yielding Strains that could eventually satisfy the need for Industrial manufacturing of isepamicin.
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enhanced single step bioproduction of the simvastatin precursor monacolin j in an Industrial Strain of aspergillus terreus by employing the evolved lovastatin hydrolase
Biotechnology Journal, 2018Co-Authors: Bo Liang, Yong Yang, Xuenian Huang, Yajing Liang, Yun Teng, Linghui ZhengAbstract:Biosynthesis of simvastatin, the active pharmaceutical ingredient of cholesterol-lowering drug Zocor, has drawn increasing global attention in recent years. Although single-step in vivo production of monacolin J, the intermediate biosynthetic precursor of simvastatin, has been realized by utilizing lovastatin hydrolase (PcEST) in our previous study, about 5% of residual lovastatin is still a problem for Industrial production and quality control. In order to improve conversion efficiency and reduce lovastatin residues, modification of PcEST is carried out through directed evolution and a novel two-step high-throughput screening method. The mutant Q140L shows 18-fold improved whole-cell activity as compared to the wild-type, and one fold enhanced catalytic efficiency and 3 °C increased T5010 over the wild-type are observed by characterizing the purified protein. Finally, the engineered A. terreus Strain overexpressing Q140L mutant exhibited the increased conversion efficiency and the reduced lovastatin residues by comparing with A. terreus Strain overexpressing the wild-type PcEST, where almost 100% of the produced lovastatin is hydrolyzed to monacolin J. Therefore, this improved microbial cell factory can realize single-step bioproduction of monacolin J in a more efficient way, providing an attractive and eco-friendly substitute over the existing chemical synthetic routes of monacolin J and promoting complete bioproduction of simvastatin at Industrial scale.
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enhanced single step bioproduction of the simvastatin precursor monacolin j in an Industrial Strain of aspergillus terreus by employing the evolved lovastatin hydrolase
Biotechnology Journal, 2018Co-Authors: Bo Liang, Yong Yang, Xuenian Huang, Yajing Liang, Yun Teng, Linghui ZhengAbstract:Biosynthesis of simvastatin, the active pharmaceutical ingredient of cholesterol-lowering drug Zocor, has drawn increasing global attention in recent years. Although single-step in vivo production of monacolin J, the intermediate biosynthetic precursor of simvastatin, has been realized by utilizing lovastatin hydrolase (PcEST) in our previous study, about 5% of residual lovastatin is still a problem for Industrial production and quality control. In order to improve conversion efficiency and reduce lovastatin residues, modification of PcEST is carried out through directed evolution and a novel two-step high-throughput screening method. The mutant Q140L shows 18-fold improved whole-cell activity as compared to the wild-type, and one fold enhanced catalytic efficiency and 3 degrees C increased T-50(10) over the wild-type are observed by characterizing the purified protein. Finally, the engineered A. terreus Strain overexpressing Q140L mutant exhibited the increased conversion efficiency and the reduced lovastatin residues by comparing with A. terreus Strain overexpressing the wild-type PcEST, where almost 100% of the produced lovastatin is hydrolyzed to monacolin J. Therefore, this improved microbial cell factory can realize single-step bioproduction of monacolin J in a more efficient way, providing an attractive and eco-friendly substitute over the existing chemical synthetic routes of monacolin J and promoting complete bioproduction of simvastatin at Industrial scale.
Jaehyun Park - One of the best experts on this subject based on the ideXlab platform.
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rna guided single double gene repressions in corynebacterium glutamicum using an efficient crispr interference and its application to Industrial Strain
Microbial Cell Factories, 2018Co-Authors: Jaehyun Park, Hyojung Shin, Youngsoon UmAbstract:Background The construction of microbial cell factories requires cost-effective and rapid Strain development through metabolic engineering. Recently, RNA-guided CRISPR technologies have been developed for metabolic engineering of Industrially-relevant host.
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rna guided single double gene repressions in corynebacterium glutamicum using an efficient crispr interference and its application to Industrial Strain
Microbial Cell Factories, 2018Co-Authors: Jaehyun Park, Hyojung Shin, Sunmi Lee, Han Min WooAbstract:The construction of microbial cell factories requires cost-effective and rapid Strain development through metabolic engineering. Recently, RNA-guided CRISPR technologies have been developed for metabolic engineering of Industrially-relevant host. To demonstrate the application of the CRISPR interference (CRISPRi), we developed two-plasmid CRISPRi vectors and applied the CRISPRi in Corynebacterium glutamicum to repress single target genes and double target genes simultaneously. Four-different single genes (the pyc, gltA, idsA, and glgC genes) repressions were successfully performed using the CRISPRi vectors, resulting significant mRNA reductions of the targets compared to a control. Subsequently, the phenotypes for the target gene-repressed Strains were analyzed, showing the expected cell growth behaviors with different carbon sources. In addition, double gene repression (the idsA and glgC genes in a different order) by the CRISPRi resulted in an independent gene repression to each target gene simultaneously. To demonstrate an Industrial application of the CRISPRi, citrate synthase (CS)-targeting DM1919 (l-lysine producer) Strains with a sgRNA-gltA-r showed reduced CS activity, resulting in the improvement of l-lysine yield by 1.39-fold than the parental DM1919 (a lysine producer). Single or double gene repression were successfully performed using the CRISPRi vectors and sequence specific sgRNAs. The CRISPRi can be applied for multiplex metabolic engineering to enhanced lysine production and it will promote the further rapid development of microbial cell factories of C. glutamicum.
Liming Liu - One of the best experts on this subject based on the ideXlab platform.
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reconstruction and analysis of the Industrial Strain bacillus megaterium wsh002 genome scale in silico metabolic model
Journal of Biotechnology, 2013Co-Authors: Wei Zou, Liming Liu, Maoda Zhou, Jian ChenAbstract:A genome-scale metabolic model of Bacillus megaterium WSH002, an Industrial bacterium widely used in the vitamin C industry, was reconstructed on the basis of the genome annotation and data from the literature and biochemical databases. It comprises 1112 reactions, 993 metabolites, and 1055 genes, including 43 new annotated genes. This model was able to predict qualitatively and quantitatively the growth of B. megaterium on a range of carbon and nitrogen sources, and the results agreed well with experimental data. A gene essentiality analysis predicted a core metabolic essential gene set of 57 genes on three different media. Furthermore, conStraint-based analysis revealed that B. megaterium WSH002 is capable of producing and exporting several key metabolites, which could promote the growth of Ketogulonicigenium vulgare and 2-keto-l-gulonic acid (2-KLG) production. Here, the model represents a helpful tool for understanding and exploring this important Industrial organism.
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reconstruction and analysis of a genome scale metabolic model of the vitamin c producing Industrial Strain ketogulonicigenium vulgare wsh 001
Journal of Biotechnology, 2012Co-Authors: Wei Zou, Liming Liu, Jing Zhang, Haoru Yang, Maoda Zhou, Qiang Hua, Jian ChenAbstract:Abstract Ketogulonicigenium vulgare WSH001 is an Industrial Strain commonly used in the vitamin C producing industry. In order to acquire a comprehensive understanding of its physiological characteristics, a genome-scale metabolic model of K. vulgare WSH001, i WZ663, including 830 reactions, 649 metabolites, and 663 genes, was reconstructed by genome annotation and literature mining. This model was capable of predicting quantitatively the growth of K. vulgare under l -sorbose fermentation conditions and the results agreed well with experimental data. Furthermore, phenotypic features, such as the defect in sulfate metabolism hampering the syntheses of l -cysteine, l -methionine, coenzyme A (CoA), and glutathione, were investigated and provided an explanation for the poor growth of K. vulgare in monoculture. The model presented here provides a validated platform that can be used to understand and manipulate the phenotype of K. vulgare to further improve 2-KLG production efficiency.
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complete genome sequence of the Industrial Strain bacillus megaterium wsh 002
Journal of Bacteriology, 2011Co-Authors: Liming Liu, Jie Liu, Lei Wang, Jing Zhang, Wei Zou, Zhemin Zhou, Jian ChenAbstract:ABSTRACT Bacillus megaterium, an Industrial Strain, has been widely used in protein production and the vitamin C industry. Here we reported a finished, annotated, and compared 4.14-Mbp high-quality genome sequence of B. megaterium WSH-002, which is the companion Strain for Ketogulonicigenium vulgare in the vitamin C industry and is stocked in our laboratory.
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complete genome sequence of the Industrial Strain ketogulonicigenium vulgare wsh 001
Journal of Bacteriology, 2011Co-Authors: Liming Liu, Jingwen Zhou, Jie Liu, Lei Wang, Jing Zhang, Zhemin Zhou, Jian ChenAbstract:Ketogulonicigenium vulgare is an Industrial organism commonly used in the vitamin C industry. Here, we report the finished, annotated, and compared 3.28-Mbp high-quality genome sequence of Ketogulonicigenium vulgare WSH-001, a 2-keto-l-gulonic acid-producing Industrial Strain stocked in our laboratory.