ArticlePloS one2012
Engineering Yarrowia lipolytica to produce glycoproteins homogeneously modified with the universal Man3GlcNAc2 N-glycan core.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 55 citations in OpenAlex.
- Enhanced Antioxidant, Antifungal, and Herbicidal Activities through Bioconversion of Diosgenin byPlants (Basel, Switzerland) · 2024Article
- Study of the persistence and dynamics of recombinant mCherry-producing Yarrowia lipolytica strains in the mouse intestine using fluorescence imaging.Microbial biotechnology · 2023Article
- Production of galactosylated complex-type N-glycans in glycoengineered Saccharomyces cerevisiae.Applied microbiology and biotechnology · 2022Article
- Humanization of Yeasts for Glycan-Type End-Products.Frontiers in microbiology · 2022Review
- The Impact of Glycoengineering on the Endoplasmic Reticulum Quality Control System in Yeasts.Frontiers in molecular biosciences · 2022Review
- Review
- Customized yeast cell factories for biopharmaceuticals: from cell engineering to process scale up.Microbial cell factories · 2021Review
- Disruption of theFrontiers in microbiology · 2021Article
- Engineering of Yeast Glycoprotein Expression.Advances in biochemical engineering/biotechnology · 2021Article
- Bioreactor-Scale Strategies for the Production of Recombinant Protein in the YeastMicroorganisms · 2019Review
- Synthetic biology tools for engineering Yarrowia lipolytica.Biotechnology advances · 2018Review
- Engineering Yarrowia lipolytica for Use in Biotechnological Applications: A Review of Major Achievements and Recent Innovations.Molecular biotechnology · 2018Review
- Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives.Advanced drug delivery reviews · 2017Review
- Effects of Rho1, a small GTPase on the production of recombinant glycoproteins in Saccharomyces cerevisiae.Microbial cell factories · 2016Article
- N-glycoprotein macroheterogeneity: biological implications and proteomic characterization.Glycoconjugate journal · 2016Review
- Engineering yeast for producing human glycoproteins: where are we now?Future microbiology · 2015Article
- Using glyco-engineering to produce therapeutic proteins.Expert opinion on biological therapy · 2015Review
- Optimized invertase expression and secretion cassette for improving Yarrowia lipolytica growth on sucrose for industrial applications.Journal of industrial microbiology & biotechnology · 2013Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Yarrowia lipolytica is a dimorphic yeast that efficiently secretes various heterologous proteins and is classified as "generally recognized as safe." Therefore, it is an attractive protein production host. However, yeasts modify glycoproteins with non-human high mannose-type N-glycans. These structures reduce the protein half-life in vivo and can be immunogenic in man. Here, we describe how we genetically engineered N-glycan biosynthesis in Yarrowia lipolytica so that it produces Man(3)GlcNAc(2) structures on its glycoproteins. We obtained unprecedented levels of homogeneity of this glycanstructure. This is the ideal starting point for building human-like sugars. Disruption of the ALG3 gene resulted in modification of proteins mainly with Man(5)GlcNAc(2) and GlcMan(5)GlcNAc(2) glycans, and to a lesser extent with Glc(2)Man(5)GlcNAc(2) glycans. To avoid underoccupancy of glycosylation sites, we concomitantly overexpressed ALG6. We also explored several approaches to remove the terminal glucose residues, which hamper further humanization of N-glycosylation; overexpression of the heterodimeric Apergillus niger glucosidase II proved to be the most effective approach. Finally, we overexpressed an α-1,2-mannosidase to obtain Man(3)GlcNAc(2) structures, which are substrates for the synthesis of complex-type glycans. The final Yarrowia lipolytica strain produces proteins glycosylated with the trimannosyl core N-glycan (Man(3)GlcNAc(2)), which is the common core of all complex-type N-glycans. All these glycans can be constructed on the obtained trimannosyl N-glycan using either in vivo or in vitro modification with the appropriate glycosyltransferases. The results demonstrate the high potential of Yarrowia lipolytica to be developed as an efficient expression system for the production of glycoproteins with humanized glycans.
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