ArticleApplied and environmental microbiology2007
Production of recombinant beta-hexosaminidase A, a potential enzyme for replacement therapy for Tay-Sachs and Sandhoff diseases, in the methylotrophic yeast Ogataea minuta.
Article in Applied and environmental microbiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 60 citations in OpenAlex.
- Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health.Nature communications · 2025Article
- Advances in Diagnosis, Pathological Mechanisms, Clinical Impact, and Future Therapeutic Perspectives in Tay-Sachs Disease.Neurology international · 2025Review
- The MFα signal sequence in yeast-based protein secretion: challenges and innovations'.Applied microbiology and biotechnology · 2025Review
- Yeast-Produced Human Recombinant Lysosomal β-Hexosaminidase Efficiently Rescues GM2 Ganglioside Accumulation in Tay-Sachs Disease.Journal of personalized medicine · 2025Article
- Production of Domain 9 from the cation-independent mannose-6-phosphate receptor fused with an Fc domain.Glycoconjugate journal · 2024Article
- Therapeutic Strategies For Tay-Sachs Disease.Frontiers in pharmacology · 2022Review
- Surface plasmon resonance analysis of complex formation of therapeutic recombinant lysosomal enzymes with domain 9 of human cation-independent mannose 6-phosphate receptor.Molecular genetics and metabolism reports · 2020Article
- Human recombinant lysosomal β-Hexosaminidases produced in Pichia pastoris efficiently reduced lipid accumulation in Tay-Sachs fibroblasts.American journal of medical genetics. Part C, Seminars in medical genetics · 2020Article
- Article
- Unusual case of Juvenile Tay-Sachs disease.BMJ case reports · 2019Article
- Neural stem cells for disease modeling and evaluation of therapeutics for Tay-Sachs disease.Orphanet journal of rare diseases · 2018Article
- New Approaches to Tay-Sachs Disease Therapy.Frontiers in physiology · 2018Review
- Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives.Advanced drug delivery reviews · 2017Review
- Efficient uptake of recombinant α-galactosidase A produced with a gene-manipulated yeast by Fabry mice kidneys.Molecular medicine (Cambridge, Mass.) · 2012Article
- Introduction of an N-glycan sequon into HEXA enhances human beta-hexosaminidase cellular uptake in a model of Sandhoff disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- GMab-1, a high-affinity anti-3'-isoLM1/3',6'-isoLD1 IgG monoclonal antibody, raised in lacto-series ganglioside-defective knockout mice.Biochemical and biophysical research communications · 2010Article
- Emerging methods for the production of homogeneous human glycoproteins.Nature chemical biology · 2009Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human beta-hexosaminidase A (HexA) is a heterodimeric glycoprotein composed of alpha- and beta-subunits that degrades GM2 gangliosides in lysosomes. GM2 gangliosidosis is a lysosomal storage disease in which an inherited deficiency of HexA causes the accumulation of GM2 gangliosides. In order to prepare a large amount of HexA for a treatment based on enzyme replacement therapy (ERT), recombinant HexA was produced in the methylotrophic yeast Ogataea minuta instead of in mammalian cells, which are commonly used to produce recombinant enzymes for ERT. The problem of antigenicity due to differences in N-glycan structures between mammalian and yeast glycoproteins was potentially resolved by using alpha-1,6-mannosyltransferase-deficient (och1Delta) yeast as the host. Genes encoding the alpha- and beta-subunits of HexA were integrated into the yeast cell, and the heterodimer was expressed together with its isozymes HexS (alphaalpha) and HexB (betabeta). A total of 57 mg of beta-hexosaminidase isozymes, of which 13 mg was HexA (alphabeta), was produced per liter of medium. HexA was purified with immobilized metal affinity column for the His tag attached to the beta-subunit. The purified HexA was treated with alpha-mannosidase to expose mannose-6-phosphate (M6P) residues on the N-glycans. The specific activities of HexA and M6P-exposed HexA (M6PHexA) for the artificial substrate 4MU-GlcNAc were 1.2 +/- 0.1 and 1.7 +/- 0.3 mmol/h/mg, respectively. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern suggested a C-terminal truncation in the beta-subunit of the recombinant protein. M6PHexA was incorporated dose dependently into GM2 gangliosidosis patient-derived fibroblasts via M6P receptors on the cell surface, and degradation of accumulated GM2 ganglioside was observed.
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