PubMed:19506294 JSON TXT

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Glycan-Motif

{"project":"Glycan-Motif","denotations":[{"id":"T1","span":{"begin":350,"end":353},"obj":"https://glytoucan.org/Structures/Glycans/G61168WC"},{"id":"T2","span":{"begin":350,"end":353},"obj":"https://glytoucan.org/Structures/Glycans/G79389NT"},{"id":"T3","span":{"begin":564,"end":567},"obj":"https://glytoucan.org/Structures/Glycans/G61168WC"},{"id":"T4","span":{"begin":564,"end":567},"obj":"https://glytoucan.org/Structures/Glycans/G79389NT"},{"id":"T5","span":{"begin":1680,"end":1683},"obj":"https://glytoucan.org/Structures/Glycans/G61168WC"},{"id":"T6","span":{"begin":1680,"end":1683},"obj":"https://glytoucan.org/Structures/Glycans/G79389NT"},{"id":"T7","span":{"begin":1893,"end":1896},"obj":"https://glytoucan.org/Structures/Glycans/G61168WC"},{"id":"T8","span":{"begin":1893,"end":1896},"obj":"https://glytoucan.org/Structures/Glycans/G79389NT"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlyCosmos6-Glycan-Motif-Image

{"project":"GlyCosmos6-Glycan-Motif-Image","denotations":[{"id":"T1","span":{"begin":350,"end":353},"obj":"Glycan_Motif"},{"id":"T3","span":{"begin":564,"end":567},"obj":"Glycan_Motif"},{"id":"T5","span":{"begin":1680,"end":1683},"obj":"Glycan_Motif"},{"id":"T7","span":{"begin":1893,"end":1896},"obj":"Glycan_Motif"}],"attributes":[{"id":"A1","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G79389NT"},{"id":"A2","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G61168WC"},{"id":"A3","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G79389NT"},{"id":"A4","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G61168WC"},{"id":"A5","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G79389NT"},{"id":"A6","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G61168WC"},{"id":"A7","pred":"image","subj":"T7","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G79389NT"},{"id":"A8","pred":"image","subj":"T7","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G61168WC"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

sentences

GlyCosmos6-Glycan-Motif-Structure

{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":350,"end":353},"obj":"https://glytoucan.org/Structures/Glycans/G61168WC"},{"id":"T2","span":{"begin":350,"end":353},"obj":"https://glytoucan.org/Structures/Glycans/G79389NT"},{"id":"T3","span":{"begin":564,"end":567},"obj":"https://glytoucan.org/Structures/Glycans/G61168WC"},{"id":"T4","span":{"begin":564,"end":567},"obj":"https://glytoucan.org/Structures/Glycans/G79389NT"},{"id":"T5","span":{"begin":1680,"end":1683},"obj":"https://glytoucan.org/Structures/Glycans/G61168WC"},{"id":"T6","span":{"begin":1680,"end":1683},"obj":"https://glytoucan.org/Structures/Glycans/G79389NT"},{"id":"T7","span":{"begin":1893,"end":1896},"obj":"https://glytoucan.org/Structures/Glycans/G61168WC"},{"id":"T8","span":{"begin":1893,"end":1896},"obj":"https://glytoucan.org/Structures/Glycans/G79389NT"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlycoBiology-GDGDB

{"project":"GlycoBiology-GDGDB","denotations":[{"id":"_T1","span":{"begin":382,"end":386},"obj":"http://acgg.asia/db/diseases/gdgdb?con_ui=CON00055"},{"id":"_T2","span":{"begin":382,"end":386},"obj":"http://acgg.asia/db/diseases/gdgdb?con_ui=CON00056"},{"id":"_T3","span":{"begin":382,"end":386},"obj":"http://acgg.asia/db/diseases/gdgdb?con_ui=CON00057"},{"id":"_T4","span":{"begin":350,"end":368},"obj":"http://acgg.asia/db/diseases/gdgdb?con_ui=CON00055"},{"id":"_T5","span":{"begin":564,"end":582},"obj":"http://acgg.asia/db/diseases/gdgdb?con_ui=CON00055"},{"id":"_T6","span":{"begin":1893,"end":1911},"obj":"http://acgg.asia/db/diseases/gdgdb?con_ui=CON00055"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlycoBiology-PACDB

{"project":"GlycoBiology-PACDB","denotations":[{"id":"_T1","span":{"begin":847,"end":871},"obj":"http://acgg.asia/db/diseases/pacdb/lec?ids=LEC297"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

ICD10

{"project":"ICD10","denotations":[{"id":"T1","span":{"begin":350,"end":368},"obj":"http://purl.bioontology.org/ontology/ICD10/E75.0"},{"id":"T2","span":{"begin":564,"end":582},"obj":"http://purl.bioontology.org/ontology/ICD10/E75.0"},{"id":"T3","span":{"begin":1893,"end":1911},"obj":"http://purl.bioontology.org/ontology/ICD10/E75.0"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlycoBiology-FMA

uniprot-human

{"project":"uniprot-human","denotations":[{"id":"T1","span":{"begin":20,"end":39},"obj":"http://www.uniprot.org/uniprot/Q9HAR0"},{"id":"T2","span":{"begin":288,"end":307},"obj":"http://www.uniprot.org/uniprot/Q9HAR0"},{"id":"T3","span":{"begin":761,"end":780},"obj":"http://www.uniprot.org/uniprot/Q9HAR0"},{"id":"T4","span":{"begin":1216,"end":1235},"obj":"http://www.uniprot.org/uniprot/Q9HAR0"},{"id":"T5","span":{"begin":1467,"end":1486},"obj":"http://www.uniprot.org/uniprot/Q9HAR0"},{"id":"T6","span":{"begin":1758,"end":1777},"obj":"http://www.uniprot.org/uniprot/Q9HAR0"},{"id":"T7","span":{"begin":957,"end":968},"obj":"http://www.uniprot.org/uniprot/Q99484"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

uniprot-mouse

{"project":"uniprot-mouse","denotations":[{"id":"T1","span":{"begin":20,"end":39},"obj":"http://www.uniprot.org/uniprot/Q9EQQ9"},{"id":"T2","span":{"begin":288,"end":307},"obj":"http://www.uniprot.org/uniprot/Q9EQQ9"},{"id":"T3","span":{"begin":761,"end":780},"obj":"http://www.uniprot.org/uniprot/Q9EQQ9"},{"id":"T4","span":{"begin":1216,"end":1235},"obj":"http://www.uniprot.org/uniprot/Q9EQQ9"},{"id":"T5","span":{"begin":1467,"end":1486},"obj":"http://www.uniprot.org/uniprot/Q9EQQ9"},{"id":"T6","span":{"begin":1758,"end":1777},"obj":"http://www.uniprot.org/uniprot/Q9EQQ9"},{"id":"T7","span":{"begin":957,"end":968},"obj":"http://www.uniprot.org/uniprot/P38649"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlycoBiology-NCBITAXON

GO-BP

{"project":"GO-BP","denotations":[{"id":"T1","span":{"begin":25,"end":39},"obj":"http://purl.obolibrary.org/obo/GO_0004563"},{"id":"T2","span":{"begin":293,"end":307},"obj":"http://purl.obolibrary.org/obo/GO_0004563"},{"id":"T3","span":{"begin":766,"end":780},"obj":"http://purl.obolibrary.org/obo/GO_0004563"},{"id":"T4","span":{"begin":1221,"end":1235},"obj":"http://purl.obolibrary.org/obo/GO_0004563"},{"id":"T5","span":{"begin":1472,"end":1486},"obj":"http://purl.obolibrary.org/obo/GO_0004563"},{"id":"T6","span":{"begin":1763,"end":1777},"obj":"http://purl.obolibrary.org/obo/GO_0004563"},{"id":"T7","span":{"begin":54,"end":68},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T8","span":{"begin":244,"end":258},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T9","span":{"begin":730,"end":745},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T10","span":{"begin":185,"end":192},"obj":"http://purl.obolibrary.org/obo/GO_0051235"},{"id":"T11","span":{"begin":185,"end":192},"obj":"http://purl.obolibrary.org/obo/GO_0035732"},{"id":"T12","span":{"begin":833,"end":840},"obj":"http://purl.obolibrary.org/obo/GO_0007114"},{"id":"T13","span":{"begin":926,"end":935},"obj":"http://purl.obolibrary.org/obo/GO_0065007"},{"id":"T14","span":{"begin":1655,"end":1663},"obj":"http://purl.obolibrary.org/obo/GO_0009056"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GO-CC

{"project":"GO-CC","denotations":[{"id":"T1","span":{"begin":175,"end":184},"obj":"http://purl.obolibrary.org/obo/GO_0005764"},{"id":"T2","span":{"begin":459,"end":463},"obj":"http://purl.obolibrary.org/obo/GO_0018995"},{"id":"T3","span":{"begin":1628,"end":1633},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlyTouCan-IUPAC

{"project":"GlyTouCan-IUPAC","denotations":[{"id":"GlycanIUPAC_T1","span":{"begin":382,"end":386},"obj":"\"http://rdf.glycoinfo.org/glycan/G81168AE\""},{"id":"GlycanIUPAC_T2","span":{"begin":382,"end":386},"obj":"\"http://rdf.glycoinfo.org/glycan/G90684IR\""},{"id":"GlycanIUPAC_T3","span":{"begin":382,"end":386},"obj":"\"http://rdf.glycoinfo.org/glycan/G32900AW\""},{"id":"GlycanIUPAC_T4","span":{"begin":382,"end":386},"obj":"\"http://rdf.glycoinfo.org/glycan/G72029GV\""},{"id":"GlycanIUPAC_T5","span":{"begin":382,"end":386},"obj":"\"http://rdf.glycoinfo.org/glycan/G69792ST\""},{"id":"GlycanIUPAC_T6","span":{"begin":382,"end":386},"obj":"\"http://rdf.glycoinfo.org/glycan/G18081CC\""},{"id":"GlycanIUPAC_T7","span":{"begin":382,"end":386},"obj":"\"http://rdf.glycoinfo.org/glycan/G39201OW\""}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlycoBiology-Motifs

{"project":"GlycoBiology-Motifs","denotations":[{"id":"T1","span":{"begin":69,"end":78},"obj":"http://rdf.glycoinfo.org/glycan/G00027MO"},{"id":"T2","span":{"begin":259,"end":268},"obj":"http://rdf.glycoinfo.org/glycan/G00027MO"},{"id":"T3","span":{"begin":783,"end":792},"obj":"http://rdf.glycoinfo.org/glycan/G00027MO"},{"id":"T4","span":{"begin":1306,"end":1315},"obj":"http://rdf.glycoinfo.org/glycan/G00027MO"},{"id":"T5","span":{"begin":1442,"end":1451},"obj":"http://rdf.glycoinfo.org/glycan/G00027MO"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlycoBiology-Epitope

{"project":"GlycoBiology-Epitope","denotations":[{"id":"PD-GlycoEpitope-B_T1","span":{"begin":1298,"end":1305},"obj":"id"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlyCosmos15-Glycan

{"project":"GlyCosmos15-Glycan","denotations":[{"id":"T1","span":{"begin":350,"end":353},"obj":"Glycan"},{"id":"T2","span":{"begin":564,"end":567},"obj":"Glycan"},{"id":"T3","span":{"begin":1680,"end":1683},"obj":"Glycan"},{"id":"T4","span":{"begin":1893,"end":1896},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G79389NT"},{"id":"A5","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G79389NT"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/G79389NT"},{"id":"A6","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G79389NT"},{"id":"A3","pred":"glycosmos_id","subj":"T3","obj":"https://glycosmos.org/glycans/show/G79389NT"},{"id":"A7","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G79389NT"},{"id":"A4","pred":"glycosmos_id","subj":"T4","obj":"https://glycosmos.org/glycans/show/G79389NT"},{"id":"A8","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G79389NT"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

mondo_disease

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":175,"end":201},"obj":"Disease"},{"id":"T2","span":{"begin":350,"end":368},"obj":"Disease"},{"id":"T3","span":{"begin":564,"end":582},"obj":"Disease"},{"id":"T4","span":{"begin":1893,"end":1911},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0002561"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0017720"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0017720"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0017720"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

Glycan-GlyCosmos

{"project":"Glycan-GlyCosmos","denotations":[{"id":"T1","span":{"begin":350,"end":353},"obj":"Glycan"},{"id":"T2","span":{"begin":564,"end":567},"obj":"Glycan"},{"id":"T3","span":{"begin":1680,"end":1683},"obj":"Glycan"},{"id":"T4","span":{"begin":1893,"end":1896},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G79389NT"},{"id":"A5","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G79389NT"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/G79389NT"},{"id":"A6","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G79389NT"},{"id":"A3","pred":"glycosmos_id","subj":"T3","obj":"https://glycosmos.org/glycans/show/G79389NT"},{"id":"A7","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G79389NT"},{"id":"A4","pred":"glycosmos_id","subj":"T4","obj":"https://glycosmos.org/glycans/show/G79389NT"},{"id":"A8","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G79389NT"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlyCosmos15-CL

{"project":"GlyCosmos15-CL","denotations":[{"id":"T1","span":{"begin":539,"end":550},"obj":"Cell"},{"id":"T2","span":{"begin":1605,"end":1616},"obj":"Cell"},{"id":"T3","span":{"begin":1621,"end":1633},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000057"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000057"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0002319"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlyCosmos15-MONDO

{"project":"GlyCosmos15-MONDO","denotations":[{"id":"T1","span":{"begin":175,"end":201},"obj":"Disease"},{"id":"T2","span":{"begin":350,"end":368},"obj":"Disease"},{"id":"T3","span":{"begin":564,"end":582},"obj":"Disease"},{"id":"T4","span":{"begin":1893,"end":1911},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"MONDO:0002561"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"MONDO:0017720"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"MONDO:0017720"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"MONDO:0017720"}],"namespaces":[{"prefix":"MONDO","uri":"http://purl.obolibrary.org/obo/MONDO_"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlyCosmos15-UBERON

{"project":"GlyCosmos15-UBERON","denotations":[{"id":"T1","span":{"begin":539,"end":550},"obj":"Body_part"},{"id":"T2","span":{"begin":1605,"end":1616},"obj":"Body_part"},{"id":"T3","span":{"begin":1621,"end":1633},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000057"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL_0000057"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL_0002319"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlyCosmos15-Taxon

{"project":"GlyCosmos15-Taxon","denotations":[{"id":"T1","span":{"begin":14,"end":19},"obj":"Organism"},{"id":"T2","span":{"begin":108,"end":122},"obj":"Organism"},{"id":"T3","span":{"begin":282,"end":287},"obj":"Organism"},{"id":"T4","span":{"begin":439,"end":453},"obj":"Organism"},{"id":"T5","span":{"begin":583,"end":591},"obj":"Organism"},{"id":"T6","span":{"begin":847,"end":871},"obj":"Organism"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"36026"},{"id":"A3","pred":"db_id","subj":"T3","obj":"9606"},{"id":"A4","pred":"db_id","subj":"T4","obj":"36026"},{"id":"A5","pred":"db_id","subj":"T5","obj":"9606"},{"id":"A6","pred":"db_id","subj":"T6","obj":"4932"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlyCosmos15-Sentences

{"project":"GlyCosmos15-Sentences","blocks":[{"id":"T1","span":{"begin":0,"end":133},"obj":"Sentence"},{"id":"T2","span":{"begin":134,"end":269},"obj":"Sentence"},{"id":"T3","span":{"begin":270,"end":369},"obj":"Sentence"},{"id":"T4","span":{"begin":370,"end":592},"obj":"Sentence"},{"id":"T5","span":{"begin":593,"end":825},"obj":"Sentence"},{"id":"T6","span":{"begin":826,"end":1014},"obj":"Sentence"},{"id":"T7","span":{"begin":1015,"end":1127},"obj":"Sentence"},{"id":"T8","span":{"begin":1128,"end":1261},"obj":"Sentence"},{"id":"T9","span":{"begin":1262,"end":1730},"obj":"Sentence"},{"id":"T10","span":{"begin":1731,"end":1912},"obj":"Sentence"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

GlyCosmos15-FMA

{"project":"GlyCosmos15-FMA","denotations":[{"id":"T1","span":{"begin":175,"end":184},"obj":"Body_part"},{"id":"T2","span":{"begin":539,"end":550},"obj":"Body_part"},{"id":"T3","span":{"begin":1605,"end":1616},"obj":"Body_part"},{"id":"T4","span":{"begin":1621,"end":1633},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"FMA:63836"},{"id":"A2","pred":"db_id","subj":"T2","obj":"FMA:63877"},{"id":"A3","pred":"db_id","subj":"T3","obj":"FMA:63877"},{"id":"A4","pred":"db_id","subj":"T4","obj":"FMA:70333"}],"namespaces":[{"prefix":"FMA","uri":"http://purl.org/sig/ont/fma/fma"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

NCBITAXON

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":14,"end":19},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":108,"end":122},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":282,"end":287},"obj":"OrganismTaxon"},{"id":"T4","span":{"begin":439,"end":453},"obj":"OrganismTaxon"},{"id":"T5","span":{"begin":847,"end":871},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"36026"},{"id":"A3","pred":"db_id","subj":"T3","obj":"9606"},{"id":"A4","pred":"db_id","subj":"T4","obj":"36026"},{"id":"A5","pred":"db_id","subj":"T5","obj":"4932"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

Anatomy-UBERON

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":539,"end":550},"obj":"Body_part"},{"id":"T2","span":{"begin":1605,"end":1616},"obj":"Body_part"},{"id":"T3","span":{"begin":1621,"end":1633},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000057"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL_0000057"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL_0002319"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}

CL-cell

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":539,"end":550},"obj":"Cell"},{"id":"T2","span":{"begin":1605,"end":1616},"obj":"Cell"},{"id":"T3","span":{"begin":1621,"end":1633},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000057"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000057"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0002319"}],"text":"Production of human beta-hexosaminidase A with highly phosphorylated N-glycans by the overexpression of the Ogataea minuta MNN4 gene.\nEffective enzyme replacement therapy for lysosomal storage diseases requires a recombinant enzyme with highly phosphorylated N-glycans. Recombinant human beta-hexosaminidase A is a potentially therapeutic enzyme for GM2-gangliosidosis. Recombinant HexA has been produced by using the methylotrophic yeast Ogataea minuta as a host, and the purified enzyme was tested for its replacement effect on cultured fibroblasts derived from GM2-gangliosidosis patients. Although the therapeutic effect was observed, in order to obtain the higher therapeutic effect with a little dose as possible, increased phosphorylation of recombinant beta-hexosaminidase A N-glycans is suggested to be prerequisite. In the budding yeast Saccharomyces cerevisiae, the overexpression of MNN4, which encodes a positive regulator of mannosylphosphate transferase, led to increased mannosylphosphate contents. In the present study, we cloned OmMNN4, a homologous gene to ScMNN4, based on the genomic sequence of O. minuta. We overexpressed the cloned gene under the control of the alcohol oxidase promoter in a beta-hexosaminidase A-producing yeast strain. Structural analysis of pyridylamine-labeled N-glycans by high-performance liquid chromatography revealed that the overexpression of MNN4 caused a 3-fold increase in phosphorylated N-glycans of recombinant beta-hexosaminidase A. The recombinant enzyme prepared from strains overexpressing OmMNN4 was more effectively incorporated into cultured fibroblasts and neural cells, and it more rapidly degraded the accumulated GM2-ganglioside as compared to the control enzyme. These results suggest that beta-hexosaminidase A produced in a strain that overexpresses OmMNN4 will act as an effective enzyme for use in replacement therapy of GM2-gangliosidosis."}