ArticleNature biotechnology2012
A bacterial glycosidase enables mannose-6-phosphate modification and improved cellular uptake of yeast-produced recombinant human lysosomal enzymes.
Article in Nature biotechnology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 109 citations in OpenAlex.
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- Modelling human proteostasis and organelle homeostasis disorders in yeast and its application in drug discovery.FEMS yeast research · 2026Review
- A C39-like protein from methanogenic archaea: structural insights and functional divergence in β-galactose analogue degradation.Frontiers in microbiology · 2026Article
- Expression of Tailored α-N-Acetylglucosaminidase inBioengineering (Basel, Switzerland) · 2025Article
- In vivo brain delivery of BBB-enabled iduronate 2-sulfatase in rats.Fluids and barriers of the CNS · 2025Article
- Genomics of soil depth niche partitioning in the Thaumarchaeota family Gagatemarchaeaceae.Nature communications · 2023Article
- Glycosylation shapes the efficacy and safety of diverse protein, gene and cell therapies.Biotechnology advances · 2023Review
- Identification of Pseudomonas aeruginosa exopolysaccharide Psl in biofilms using 3D OrbiSIMS.Biointerphases · 2023Article
- Structural and functional characterization of a multi-domain GH92 α-1,2-mannosidase from Neobacillus novalis.Acta crystallographica. Section D, Structural biology · 2023Article
- Study of the persistence and dynamics of recombinant mCherry-producing Yarrowia lipolytica strains in the mouse intestine using fluorescence imaging.Microbial biotechnology · 2023Article
- The In Silico Characterization of Monocotyledonous α-l-Arabinofuranosidases on the Example of Maize.Life (Basel, Switzerland) · 2023Article
- PlantProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Glyco-Decipher enables glycan database-independent peptide matching and in-depth characterization of site-specific N-glycosylation.Nature communications · 2022Article
- New Opportunities in Glycan Engineering for Therapeutic Proteins.Antibodies (Basel, Switzerland) · 2022Review
- Article
- Mannose-6-phosphate glycan for lysosomal targeting: various applications from enzyme replacement therapy to lysosome-targeting chimeras.Animal cells and systems · 2022Article
- Chemoenzymatic glycan-selective remodeling of a therapeutic lysosomal enzyme with high-affinity M6P-glycan ligands. Enzyme substrate specificity is the name of the game.Chemical science · 2021Article
- Review
- Customized yeast cell factories for biopharmaceuticals: from cell engineering to process scale up.Microbial cell factories · 2021Review
- In VitroJournal of microbiology and biotechnology · 2021Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosomal storage diseases are treated with human lysosomal enzymes produced in mammalian cells. Such enzyme therapeutics contain relatively low levels of mannose-6-phosphate, which is required to target them to the lysosomes of patient cells. Here we describe a method for increasing mannose-6-phosphate modification of lysosomal enzymes produced in yeast. We identified a glycosidase from C. cellulans that 'uncaps' N-glycans modified by yeast-type mannose-Pi-6-mannose to generate mammalian-type N-glycans with a mannose-6-phosphate substitution. Determination of the crystal structure of this glycosidase provided insight into its substrate specificity. We used this uncapping enzyme together with α-mannosidase to produce in yeast a form of the Pompe disease enzyme α-glucosidase rich in mannose-6-phosphate. Compared with the currently used therapeutic version, this form of α-glucosidase was more efficiently taken up by fibroblasts from Pompe disease patients, and it more effectively reduced cardiac muscular glycogen storage in a mouse model of the disease.
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