ArticleMicrobial cell factories2011
Design of an efficient medium for heterologous protein production in Yarrowia lipolytica: case of human interferon alpha 2b.
Article in Microbial cell factories, 2011. 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, 35 citations in OpenAlex.
- Yarrowia lipolytica and Komagataella phaffii (Pichia pastoris) as Hosts for Heterologous Expression of Lipases.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Biosynthesis of Sciadonic Acid Derived from Gymnosperms with Anti-Colitis Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Defined YNB-free mineral medium improves reproducibility and enables high-titer production in Yarrowia lipolytica.Microbial cell factories · 2026Article
- 'Mother(Nature) knows best' - hijacking nature-designed transcriptional programs for enhancing stress resistance and protein production in Yarrowia lipolytica; presentation of YaliFunTome database.Microbial cell factories · 2024Article
- Comparative Analysis of the Alkaline Proteolytic Enzymes ofInternational journal of molecular sciences · 2023Article
- Study of the persistence and dynamics of recombinant mCherry-producing Yarrowia lipolytica strains in the mouse intestine using fluorescence imaging.Microbial biotechnology · 2023Article
- Hyperosmolarity adversely impacts recombinant protein synthesis by Yarrowia lipolytica-molecular background revealed by quantitative proteomics.Applied microbiology and biotechnology · 2022Article
- The Role of Hexokinase and Hexose Transporters in Preferential Use of Glucose over Fructose and Downstream Metabolic Pathways in the YeastInternational journal of molecular sciences · 2021Article
- Customized yeast cell factories for biopharmaceuticals: from cell engineering to process scale up.Microbial cell factories · 2021Review
- Cross-Feeding of a Toxic Metabolite in a Synthetic Lignocellulose-Degrading Microbial Community.Microorganisms · 2021Article
- Modulating Heterologous Pathways and Optimizing Culture Conditions for Biosynthesis ofMolecules (Basel, Switzerland) · 2019Article
- Bioreactor-Scale Strategies for the Production of Recombinant Protein in the YeastMicroorganisms · 2019Review
- Filamentous fungi-like secretory pathway strayed in a yeast system: peculiarities of Yarrowia lipolytica secretory pathway underlying its extraordinary performance.Applied microbiology and biotechnology · 2019Review
- Deciphering how LIP2 and POX2 promoters can optimally regulate recombinant protein production in the yeast Yarrowia lipolytica.Microbial cell factories · 2016Article
- Draft Genome Sequence of the Oleaginous Yeast Yarrowia lipolytica PO1f, a Commonly Used Metabolic Engineering Host.Genome announcements · 2014Article
- Development of a cultivation process for the enhancement of human interferon alpha 2b production in the oleaginous yeast, Yarrowia lipolytica.Microbial cell factories · 2011Article
- Biotransformation of acetophenone and its halogen derivatives byAnnals of microbiologyArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe non conventional yeast Yarrowia lipolytica has aroused a strong industrial interest for heterologous protein production. However most of the studies describing recombinant protein production by this yeast rely on the use of complex media, such media are not convenient for large scale production particularly for products intended for pharmaceutical applications. In addition medium composition can also affect the production yield. Hence it is necessary to design an efficient medium for therapeutic protein expression by this host.
resultsFive different media, including four minimal media and a complex medium, were assessed in shake flasks for the production of human interferon alpha 2b (hIFN α2b) by Y. lipolytica under the control of POX2 promoter inducible with oleic acid. The chemically defined medium SM4 formulated by Invitrogen for Pichia pastoris growth was the most suitable. Using statistical experimental design this medium was further optimized. The selected minimal medium consisting in SM4 supplemented with 10 mg/l FeCl₃, 1 g/l glutamate, 5 ml/l PTM1 (Pichia Trace Metals) solution and a vitamin solution composed of myo-inositol, thiamin and biotin was called GNY medium. Compared to shake flask, bioreactor culture in GNY medium resulted in 416-fold increase of hIFN α2b production and 2-fold increase of the biological activity. Furthermore, SM4 enrichment with 5 ml/l PTM1 solution contributed to protect hIFN α2b against the degradation by the 28 kDa protease identified by zymography gel in culture supernatant. The screening of the inhibitory effect of the trace elements present in PTM1 solution on the activity of this protease was achieved using a Box-Behnken design. Statistical data analysis showed that FeCl₃ and MnSO₄ had the most inhibitory effect.
conclusionWe have designed an efficient medium for large scale production of heterologous proteins by Y. lipolytica. The optimized medium GNY is suitable for the production of hIFN α2b with the advantage that no complex nitrogen sources with non-defined composition were required.
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