Skip to main content

Heterologous Protein Expression and Secretion in Yarrowia lipolytica

  • Chapter
  • First Online:
Yarrowia lipolytica

Part of the book series: Microbiology Monographs ((MICROMONO,volume 25))

Abstract

Heterologous protein production constitutes an important research field, having both academic and commercial applications. The use of yeasts as host systems took advantage of the combination of their easy manipulation and high growth capacity, with their eukaryotic subcellular organisation allowing post-translational processing. Among available yeast host systems, Yarrowia lipolytica (Yarrowia) appears as one of the most attractive. This non-conventional dimorphic yeast has been distinguished due to its remarkable regularity of performance in the efficient secretion of various heterologous proteins. We will present in this chapter Yarrowia’s characteristics regarding heterologous protein production and describe the genetic and molecular tools available. Recent developments of the Yarrowia expression system, such as surface display vectors, engineered strains and high-throughput screening processes, will be reviewed. A comprehensive survey of the literature allowed us to list more than 100 heterologous proteins, from more than 60 species, successfully produced until now in this yeast. This amount of data sometimes offers a comparison with other yeast host systems and globally demonstrates the reliability and versatility of Yarrowia as host for heterologous production.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aitchison JD, Murray WW, Rachubinski RA (1991) The carboxyl-terminal tripeptide Ala-Lys-Ile is essential for targeting Candida tropicalis trifunctional enzyme to yeast peroxisomes. J Biol Chem 266(34):23197–23203

    PubMed  CAS  Google Scholar 

  • Alkasrawi M, Nandakumar R, Margesin R, Schinner F, Mattiasson B (1999) A microbial biosensor based on Yarrowia lipolytica for the off-line determination of middle-chain alkanes. Biosens Bioelectron 14(8–9):723–727

    Article  PubMed  CAS  Google Scholar 

  • Babour A, Beckerich JM, Gaillardin C (2004) Identification of an UDP-Glc:glycoprotein glucosyltransferase in the yeast Yarrowia lipolytica. Yeast 21:11–24

    Article  PubMed  CAS  Google Scholar 

  • Bankar AV, Kumar AR, Zinjarde SS (2009) Environmental and industrial applications of Yarrowia lipolytica. Appl Microbiol Biotechnol 84(5):847–865

    Article  PubMed  CAS  Google Scholar 

  • Barnay-Verdier S, BoisramĂ© A, Beckerich JM (2004) Identification and characterization of two alpha-1,6-mannosyltransferases, Anl1p and Och1p, in the yeast Yarrowia lipolytica. Microbiology 150:2185–2195

    Article  PubMed  CAS  Google Scholar 

  • Barnay-Verdier S, Beckerich JM, BoisramĂ© A (2008) New components of Yarrowia lipolytica Golgi multi-protein complexes containing the alpha-1,6-mannosyltransferases YlMnn9p and YlAnl1p. Curr Genet 54(6):313–323

    Article  PubMed  CAS  Google Scholar 

  • Barth G, Gaillardin C (1996) Yarrowia lipolytica. In: Wolf K (ed) Nonconventional yeasts in biotechnology: a handbook. Springer, Heidelberg, pp 313–388

    Chapter  Google Scholar 

  • Barth G, Gaillardin C (1997) Physiology and genetics of the dimorphic fungus Yarrowia lipolytica. FEMS Microbiol Rev 19:219–237

    Article  PubMed  CAS  Google Scholar 

  • Bauer R, Paltauf F, Kohlwein SD (1993) Functional expression of bacterial β-glucuronidase and its use as a reporter system in the yeast Yarrowia lipolytica. Yeast 9:71–75

    Article  PubMed  CAS  Google Scholar 

  • Beckerich JM, BoisramĂ©-Baudevin A, Gaillardin C (1998) Yarrowia lipolytica: a model organism for protein secretion studies. Int Microbiol 1:123–130

    PubMed  CAS  Google Scholar 

  • Bhave SL, Chattoo BB (2003) Expression of Vitreoscilla hemoglobin improves growth and levels of extracellular enzyme in Yarrowia lipolytica. Biotechnol Bioeng 84(6):658–666

    Article  PubMed  CAS  Google Scholar 

  • Bilyeu KD, Cole JL, Laskey JG, Riekhof WR, Esparza TJ, Kramer MD, Morris RO (2001) Molecular and biochemical characterization of a cytokinin oxidase from maize. Plant Physiol 125:378–386

    Article  PubMed  CAS  Google Scholar 

  • Blanchin-Roland S, Cordero Otero R, Gaillardin C (1994) Two upstream activation sequences control the expression of the XPR2 gene in the yeast Yarrowia lipolytica. Mol Cell Biol 14:327–338

    PubMed  CAS  Google Scholar 

  • Blazeck J, Liu L, Redden H, Alper H (2011) Tuning gene expression in Yarrowia lipolytica by a hybrid promoter approach. Appl Environ Microbiol 77(22):7905–7914

    Article  PubMed  CAS  Google Scholar 

  • Boer E, Steinborn G, Matros A, Mock HP, Gellissen G, Kunze G (2007) Production of interleukin-6 in Arxula adeninivorans, Hansenula polymorpha and Saccharomyces cerevisiae by applying the wide-range yeast vector (CoMed) system to simultaneous comparative assessment. FEMS Yeast Res 7(7):1181–1187

    Article  PubMed  CAS  Google Scholar 

  • Boer E, Piontek M, Kunze G (2009) Xplor 2 – an optimized transformation/expression system for recombinant protein production in the yeast Arxula adeninivorans. Appl Microbiol Biotechnol 84(3):583–594

    Article  PubMed  CAS  Google Scholar 

  • BoisramĂ© A, Gaillardin C (2009) Heterologous expression and characterization of a beta-1, 6-glucanase from Aspergillus fumigatus. Appl Microbiol Biotechnol 82(4):663–669

    Article  PubMed  CAS  Google Scholar 

  • BoisramĂ© A, Kabani M, Beckerich JM, Hartmann E, Gaillardin C (1998) Interaction of Kar2p and Sls1p is required for efficient co-translational translocation of secreted proteins in the yeast Yarrowia lipolytica. J Biol Chem 273(47):30903–30908

    Article  PubMed  Google Scholar 

  • Bordes F, Fudalej F, Dossat V, Nicaud JM, Marty A (2007) A new recombinant protein expression system for high-throughput screening in the yeast Yarrowia lipolytica. J Microbiol Methods 70(3):493–502

    Article  PubMed  CAS  Google Scholar 

  • Bourel G, Nicaud JM, Nthangeni B, Santiago-Gomez P, Belin JM, Husson F (2004) Fatty acid hydroperoxide lyase of the green bell pepper : cloning in Yarrowia lipolytica and biogenesis of volatile aldehydes. Enzyme Microb Technol 35:293–299

    Article  CAS  Google Scholar 

  • Brown JD, Hann BC, Medzihradszky KF, Niwa M, Burlingame AL, Walter P (1994) Subunits of the Saccharomyces cerevisiae signal recognition particle required for its functional expression. EMBO J 13(18):4390–4400

    PubMed  CAS  Google Scholar 

  • Buckholz RG, Gleeson MAG (1991) Yeast systems for the commercial production of heterologous proteins. Biotechnology 9:1067–1072

    Article  PubMed  CAS  Google Scholar 

  • Butinar L, Santos S, Spencer-Martins I, Oren A, Gunde-Cimerman N (2005) Yeast diversity in hypersaline habitats. FEMS Microbiol Lett 244:229–234

    Article  PubMed  CAS  Google Scholar 

  • Casaregola S, Feynerol C, Diez M, Fournier P, Gaillardin C (1997) Genomic organization of the yeast Yarrowia lipolytica. Chromosoma 106:380–390

    Article  PubMed  CAS  Google Scholar 

  • Casaregola S, NeuvĂ©glise C, LĂ©pingle A, Bon E, Feynerol C, Artiguenave F, Winckler P, Gaillardin C (2000) Genomic exploration of the hemiascomycetous yeasts: 17. Yarrowia lipolytica. FEBS Lett 487:95–100

    Article  PubMed  CAS  Google Scholar 

  • Cereghino JL, Cregg JM (2000) Heterologous protein expression in the methylotrophic yeast Pichia pastoris. FEMS Microbiol Rev 24:45–66

    Article  PubMed  CAS  Google Scholar 

  • Cereghino GPL, Cereghino JL, Ilgen C, Cregg JM (2002) Production of recombinant proteins in fermenter cultures of the yeast Pichia pastoris. Curr Opin Biotechnol 13:329–332

    Article  PubMed  Google Scholar 

  • Chang CC, Ryu DD, Park CS, Kim JY (1998) Improvement of heterologous protein productivity using recombinant Yarrowia lipolytica and cyclic fed-batch process strategy. Biotechnol Bioeng 59(3):379–385

    Article  PubMed  CAS  Google Scholar 

  • Chen GQ, Wu Q (2005) The application of polyhydroxyalkanoates as tissue engineering materials. Biomaterials 26:6565–6578

    Article  PubMed  CAS  Google Scholar 

  • Chen DC, Beckerich JM, Gaillardin C (1997) One-step transformation of the dimorphic yeast Yarrowia lipolytica. Appl Microbiol Biotechnol 48(2):232–235

    Article  PubMed  CAS  Google Scholar 

  • Chi ZM, Chi Z, Zhang T, Liu GL, Yue LX (2009) Inulinase expressing microorganisms and applications of inulinases. Appl Microbiol Biotechnol 82:211–220

    Article  PubMed  CAS  Google Scholar 

  • Cho EM, Lee HS, Eom CY, Ohta A (2010) Construction of high sensitive detection system for endocrine disruptors with yeast n-alkane-assimilating Yarrowia lipolytica. J Microbiol Biotechnol 20(11):1563–1570

    Article  PubMed  CAS  Google Scholar 

  • Chuang LT, Chen DZ, Chen YH, Nicaud JM, Madzak C, Huang YS (2009) Production of functional alpha-linolenic acid (GLA) by expression of fungal delta12- and delta6-desaturases genes in the oleaginous yeast Yarrowia lipolytica. In: Hou CT, Shaw JF (eds) Biocatalysis and agricultural biotechnology. CRC, Boca Raton, pp 163–180

    Google Scholar 

  • Chuang LT, Chen DC, Nicaud JM, Madzak C, Chen YH, Huang YS (2010) Co-expression of heterologous desaturase genes in Yarrowia lipolytica. N Biotechnol 27(4):277–282

    Article  PubMed  CAS  Google Scholar 

  • Cordero Otero R, Gaillardin C (1996) Efficient selection of hygromycin-B-resistant Yarrowia lipolytica transformants. Appl Microbiol Biotechnol 46:143–148

    Article  PubMed  CAS  Google Scholar 

  • Cregg JM, Cereghino JL, Shi J, Higgins DR (2000) Recombinant protein expression in Pichia pastoris. Mol Biotechnol 16:23–52

    Article  PubMed  CAS  Google Scholar 

  • Cui W, Wang Q, Zhang F, Zhang SC, Chi ZM, Madzak C (2011) Direct conversion of inulin into single cell protein by the engineered Yarrowia lipolytica carrying inulinase gene. Process Biochem 46(7):1442–1448

    Article  CAS  Google Scholar 

  • Das UN (2008) Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules. Lipids Health Dis 7:37–54

    Article  PubMed  CAS  Google Scholar 

  • Davidow LS, Dezeeuw JR (1985) Process for transformation of Yarrowia lipolytica. European Patent Application EP0138508 (A1)

    Google Scholar 

  • Davidow LS, Franke AE, De Zeeuw JR (1987a) Expression and secretion of heterologous proteins by Yarrowia lipolytica transformants. European Patent Application EP0220864 (A1)

    Google Scholar 

  • Davidow LS, Franke AE, De Zeeuw JR (1987b) New Yarrowia lipolytica transformants used for expression and secretion of heterologous proteins, especially prorennin and human anaphylatoxin C5a. European Patent Application EP86307839 (A1)

    Google Scholar 

  • Davidow LS, O’Donnell MM, Kaczmarek FS, Pereira DA, DeZeeuw JR, Franke AE (1987c) Cloning and sequencing of the alkaline extracellular protease gene of Yarrowia lipolytica. J Bacteriol 169(10):4621–4629

    PubMed  CAS  Google Scholar 

  • De Baetselier A, Vasavada A, Dohet P, Ha-Thi V, De Beukelaer M, Erpicum T, De Clerck L, Hanotier J, Rosemberg S (1991) Fermentation of a yeast producing A. niger glucose oxidase: scale-up, purification and characterization of the recombinant enzyme. Biotechnology 9:559–561

    Article  PubMed  Google Scholar 

  • Dean N (1999) Asparagine-linked glycosylation in the yeast Golgi. Biochim Biophys Acta 1426:309–322

    Article  PubMed  CAS  Google Scholar 

  • Dominguez A, Ferminan E, Sanchez M, Gonzalez FJ, Perez-Campo FM, Garcia S, Herrero AB, San Vicente A, Cabello J, Prado M, Iglesias FJ, Choupina A, Burguillo FJ, Fernandez-Lago L, Lopez MC (1998) Non-conventional yeasts as hosts for heterologous protein production. Int Microbiol 1:131–142

    PubMed  CAS  Google Scholar 

  • Dominguez A, Ferminan E, Gaillardin C (2000) Yarrowia lipolytica: an organism amenable to genetic manipulation as a model for analyzing dimorphism in fungi. Contrib Microbiol 5:151–172

    Article  PubMed  CAS  Google Scholar 

  • Dujon B, Sherman D, Fischer G, Durrens P, Casaregola S, Lafontaine I, De Montigny J, Marck C, Neuveglise C, Talla E, Goffard N, Frangeul L, Aigle M, Anthouard V, Babour A, Barbe V, Barnay S, Blanchin S, Beckerich JM, Beyne E, Bleykasten C, Boisrame A, Boyer J, Cattolico L, Confanioleri F, De Daruvar A, Despons L, Fabre E, Fairhead C, Ferry-Dumazet H, Groppi A, Hantraye F, Hennequin C, Jauniaux N, Joyet P, Kachouri R, Kerrest A, Koszul R, Lemaire M, Lesur I, Ma L, Muller H, Nicaud JM, Nikolski M, Oztas S, Ozier-Kalogeropoulos O, Pellenz S, Potier S, Richard GF, Straub ML, Suleau A, Swennen D, Tekaia F, Wesolowski-Louvel M, Westhof E, Wirth B, Zeniou-Meyer M, Zivanovic I, Bolotin-Fukuhara M, Thierry A, Bouchier C, Caudron B, Scarpelli C, Gaillardin C, Weissenbach J, Wincker P, Souciet JL (2004) Genome evolution in yeasts. Nature 430:35–44

    Article  PubMed  Google Scholar 

  • Emond S, Montanier C, Nicaud JM, Marty A, Monsan P, AndrĂ© I, Remaud-SimĂ©on M (2010) New efficient recombinant expression system to engineer Candida antarctica lipase B. Appl Environ Microbiol 76(8):2684–2687

    Article  PubMed  CAS  Google Scholar 

  • Fabre E, Nicaud JM, Lopez MC, Gaillardin C (1991) Role of the proregion in the production and secretion of the Yarrowia lipolytica alkaline extracellular protease. J Biol Chem 266:3782–3790

    PubMed  CAS  Google Scholar 

  • Fabre E, Tharaud C, Gaillardin C (1992) Intracellular transit of a yeast protease is rescued by trans-complementation with its prodomain. J Biol Chem 267:15049–15055

    PubMed  CAS  Google Scholar 

  • Fickers P, Le Dall MT, Gaillardin C, Thonart P, Nicaud JM (2003) New disruption cassettes for rapid gene disruption and marker rescue in the yeast Yarrowia lipolytica. J Microbiol Methods 55(3):727–737

    Article  PubMed  CAS  Google Scholar 

  • Fickers P, Benetti PH, Wache Y, Marty A, Mauersberger S, Smit MS, Nicaud JM (2005) Hydrophobic substrate utilisation by the yeast Yarrowia lipolytica, and its potential applications. FEMS Yeast Res 5:527–543

    Article  PubMed  CAS  Google Scholar 

  • Flagfeldt DB, Siewers V, Huang L, Nielsen J (2009) Characterization of chromosomal integration sites for heterologous gene expression in Saccharomyces cerevisiae. Yeast 26(10):545–551

    Article  PubMed  CAS  Google Scholar 

  • Fournier P, Guyaneux L, Chasles M, Gaillardin C (1991) Scarcity of ARS sequences isolated in a morphogenesis mutant of the yeast Yarrowia lipolytica. Yeast 7:25–36

    Article  PubMed  CAS  Google Scholar 

  • Fournier P, Abbas A, Chasles M, Kudla B, Ogrydziak DM, Yaver D, Xuan JW, Peito A, Ribet AM, Feynerol C, He F, Gaillardin C (1993) Colocalization of centromeric and replicative functions on autonomously replicating sequences isolated from the yeast Yarrowia lipolytica. Proc Natl Acad Sci USA 90:4912–4916

    Article  PubMed  CAS  Google Scholar 

  • Franke AE, Kaczmarek FS, Eisenhard ME, Geoghegan KF, Danley DE, De Zeeuw JR, O’Donnell MM, Gollaher MG, Davidow LS (1988) Expression and secretion of bovine prochymosin in Yarrowia lipolytica. In: Pierce G (ed) Developments in industrial microbiology, vol 29. Elsevier, Amsterdam, pp 43–57

    Google Scholar 

  • Fretland AJ, Omiecinski CJ (2000) Epoxide hydrolases: biochemistry and molecular biology. Chem Biol Interact 129(1–2):41–59

    Article  PubMed  CAS  Google Scholar 

  • Gaillardin C, Ribet AM (1987) LEU2 directed expression of β-galactosidase activity and phleomycin resistance in Yarrowia lipolytica. Curr Genet 11:369–375

    Article  PubMed  CAS  Google Scholar 

  • Gaillardin C, Heslot H, Ribet AM (1985) Vecteur de transformation de la levure Yarrowia lipolytica, procĂ©dĂ© de transformation et levure transformĂ©e. French Patent Application FR2566424 (A1)

    Google Scholar 

  • Galli C, Gentili P, Jolivalt C, Madzak C, VadalĂ  R (2011) How is the reactivity of laccase affected by single-point mutations? Engineering laccase for improved activity towards sterically demanding substrates. Appl Microbiol Biotechnol 91(1):123–131

    Article  PubMed  CAS  Google Scholar 

  • Gasmi N, Fudalej F, Kallel H, Nicaud JM (2011a) A molecular approach to optimize hIFN α2b expression and secretion in Yarrowia lipolytica. Appl Microbiol Biotechnol 89(1):109–119

    Article  PubMed  CAS  Google Scholar 

  • Gasmi N, Ayed A, Nicaud JM, Kallel H (2011b) Design of an efficient medium for heterologous protein production in Yarrowia lipolytica: case of human interferon alpha 2b. Microb Cell Fact 10:38–50

    Article  PubMed  CAS  Google Scholar 

  • Gasmi N, Ayed A, Ammar BB, Zrigui R, Nicaud JM, Kallel H (2011c) Development of a cultivation process for the enhancement of human interferon alpha 2b production in the oleaginous yeast, Yarrowia lipolytica. Microb Cell Fact 10:90–100

    Article  PubMed  CAS  Google Scholar 

  • Gellisen G, Hollenberg CP (1997) Applications of yeast in gene expression studies: a comparison of Saccharomyces cerevisiae, Hansenula polymorpha and Kluyveromyces lactis – a review. Gene 190:87–97

    Article  Google Scholar 

  • Gellissen G, Kunze G, Gaillardin C, Cregg JM, Berardi E, Veenhuis M, van der Klei I (2005) New yeast expression platforms based on methylotrophic Hansenula polymorpha and Pichia pastoris and on dimorphic Arxula adeninivorans and Yarrowia lipolytica – a comparison. FEMS Yeast Res 5(11):1079–1096

    Article  PubMed  CAS  Google Scholar 

  • Goochee CF, Gramer MJ, Andersen DC, Bahr JB, Rasmussen JR (1991) The oligosaccharides of glycoproteins: bioprocess factors affecting oligosaccharide structure and their effect on glycoprotein properties. Biotechnology 9:1347–1355

    Article  PubMed  CAS  Google Scholar 

  • Grinna LS, Tschopp JF (1989) Size distribution and general structural features of N-linked oligosaccharides from the methylotrophic yeast Pichia pastoris. Yeast 5:107–115

    Article  PubMed  CAS  Google Scholar 

  • Haddouche R, Delessert S, Sabirova J, NeuvĂ©glise C, Poirier Y, Nicaud JM (2010) Roles of multiple acyl-CoA oxidases in the routing of carbon flow towards β-oxidation and polyhydroxyalkanoate biosynthesis in Yarrowia lipolytica. FEMS Yeast Res 10(7):917–927

    Article  PubMed  CAS  Google Scholar 

  • Haddouche R, Poirier Y, Delessert S, Sabirova J, Pagot Y, NeuvĂ©glise C, Nicaud JM (2011) Engineering polyhydroxyalkanoate content and monomer composition in the oleaginous yeast Yarrowia lipolytica by modifying the Ăź-oxidation multifunctional protein. Appl Microbiol Biotechnol 91(5):1327–1340

    Article  PubMed  CAS  Google Scholar 

  • Hamilton SR, Gerngross TU (2007) Glycosylation engineering in yeast: the advent of fully humanized yeast. Curr Opin Biotechnol 18(5):387–392

    Article  PubMed  CAS  Google Scholar 

  • Hamilton SR, Davidson RC, Sethuraman N, Nett JH, Jiang Y, Rios S, Bobrowicz P, Stadheim TA, Li H, Choi BK, Hopkins D, Wischnewski H, Roser J, Mitchell T, Strawbridge RR, Hoopes J, Wildt S, Gerngross TU (2006) Humanization of yeast to produce complex terminally sialylated glycoproteins. Science 313:1441–1443

    Article  PubMed  CAS  Google Scholar 

  • Hamsa PV, Chattoo BB (1994) Cloning and growth-regulated expression of the gene encoding the hepatitis B virus middle surface antigen in Yarrowia lipolytica. Gene 143:165–170

    Article  PubMed  CAS  Google Scholar 

  • Hamsa PV, Kachroo P, Chattoo BB (1998) Production and secretion of biologically active human epidermal growth factor in Yarrowia lipolytica. Curr Genet 33:231–237

    Article  PubMed  CAS  Google Scholar 

  • He F, Beckerich JM, Gaillardin C (1992) A mutant of 7SL RNA in Yarrowia lipolytica affecting the synthesis of a secreted protein. J Biol Chem 267(3):1932–1937

    PubMed  CAS  Google Scholar 

  • Hong SP, Sharpe P, Xue Z, Yadav N, Zhu Q (2009) High eicosapentaenoic acid oils from improved strains of Yarrowia lipolytica. World Patent Application WO2010147907 (A1)

    Google Scholar 

  • Hong SP, Seip J, Walters-Pollak D, Rupert R, Jackson R, Xue Z, Zhu Q (2012) Engineering Yarrowia lipolytica to express secretory invertase with strong FBA1(IN) promoter. Yeast 29:59–72

    Article  CAS  Google Scholar 

  • Huang YC, Chen YF, Chen CY, Chen WL, Ciou YP, Liu WH, Yang CH (2011) Production of ferulic acid from lignocellulolytic agricultural biomass by Thermobifida fusca thermostable esterase produced in Yarrowia lipolytica transformant. Bioresour Technol 102(17):8117–8122

    Article  PubMed  CAS  Google Scholar 

  • Jaafar L, Zueco J (2004) Characterization of a glycosylphosphatidylinositol-bound cell-wall protein (GPI-CWP) in Yarrowia lipolytica. Microbiology 150(Pt 1):53–60

    Article  PubMed  CAS  Google Scholar 

  • Jaafar L, Leon M, Zueco J (2003) Identification of the MNN9 gene of Yarrowia lipolytica (YlMNN9) and phenotype analysis of a mutant ylmnn9Δ strain. Yeast 20:633–644

    Article  PubMed  CAS  Google Scholar 

  • James L, Strick C (1995) Multiple integrative vectors and Yarrowia lipolytica transformants. World Patent Application WO9506739 (A1)

    Google Scholar 

  • Jigami Y, Odani T (1999) Mannosylphosphate transfer to yeast mannan. Biochim Biophys Acta 1426(2):335–345

    Article  PubMed  CAS  Google Scholar 

  • Jolivalt C, Madzak C, Brault A, Caminade E, Malosse C, Mougin C (2005) Expression of laccase IIIb from the white-rot fungus Trametes versicolor in the yeast Yarrowia lipolytica for environmental applications. Appl Microbiol Biotechnol 66(4):450–456

    Article  PubMed  CAS  Google Scholar 

  • Jolivet P, Bordes F, Fudalej F, Cancino M, Vignaud C, Dossat V, Burghoffer C, Marty A, Chardot T, Nicaud JM (2007) Analysis of Yarrowia lipolytica extracellular lipase Lip2p glycosylation. FEMS Yeast Res 7(8):1317–1327

    Article  PubMed  CAS  Google Scholar 

  • Juretzek T, Wang HJ, Nicaud JM, Mauersberger S, Barth G (2000a) Comparison of promoters suitable for regulated overexpression of β-galactosidase in the alkane-utilizing yeast Yarrowia lipolytica. Biotechnol Bioprocess Eng 5:320–326

    Article  CAS  Google Scholar 

  • Juretzek T, Mauersberger S, Barth G (2000b) Recombinant haploid or diploid Yarrowia lipolytica cells for the functional heterologous expression of cytochrome P450 systems. World Patent Application WO0003008

    Google Scholar 

  • Juretzek T, Le Dall M, Mauersberger S, Gaillardin C, Barth G, Nicaud JM (2001) Vectors for gene expression and amplification in the yeast Yarrowia lipolytica. Yeast 18:97–113

    Article  PubMed  CAS  Google Scholar 

  • Kim JW, Park TJ, Ryu DD, Kim JY (2000) High cell density culture of Yarrowia lipolytica using a one-step feeding process. Biotechnol Prog 16(4):657–660

    Article  PubMed  CAS  Google Scholar 

  • Kim MW, Rhee SK, Kim JY, Shimma Y, Chiba Y, Jigami Y, Kang HA (2004) Characterization of N-linked oligosaccharides assembled on secretory recombinant glucose oxidase and cell wall mannoproteins from the methylotrophic yeast Hansenula polymorpha. Glycobiology 14(3):243–251

    Article  PubMed  CAS  Google Scholar 

  • Kopecny D, Briozzo P, Joly N, Houba-HĂ©rin N, Madzak C, Pethe C, Laloue M (2004) Purification, crystallization and preliminary X-ray diffraction study of a recombinant cytokinin oxidase from Zea mays. Acta Crystallogr D Biol Crystallogr 60(8):1500–1501

    Article  PubMed  CAS  Google Scholar 

  • Kopecny D, Pethe C, Sebela M, Houba-HĂ©rin N, Madzak C, Majira A, Laloue M (2005) High-level expression and characterization of Zea mays cytokinin oxidase/dehydrogenase in Yarrowia lipolytica. Biochimie 87(11):1011–1022

    Article  PubMed  CAS  Google Scholar 

  • Kopecny D, Popelkova H, Madzak C, Briozzo P, Sebela M, FrĂ©bort I, Majira A, Laloue M, Houba-HĂ©rin N (2008) Site-directed mutagenesis of maize cytokinin oxidase/dehydrogenase. Physiol Plant 133(S3):189–190

    Google Scholar 

  • Kopecny D, Briozzo P, Popelkova H, Sebela M, Koncitikova R, Spichal L, Nisler J, Madzak C, FrĂ©bort I, Laloue M, Houba-HĂ©rin N (2010) Phenyl- and benzylurea cytokinins as competitive inhibitors of cytokinin oxidase/dehydrogenase: a structural study. Biochimie 92(8):1052–1062

    Article  PubMed  CAS  Google Scholar 

  • Kozak M (1999) Initiation of translation in prokaryotes and eukaryotes. Gene 234(2):187–208

    Article  PubMed  CAS  Google Scholar 

  • LabuschagnĂ© M (2005) Cloning and expression of epoxide hydrolases: Yarrowia lipolytica as an attractive heterologous expression host. PhD Thesis, University of Free State, Bloemfontein, South Africa

    Google Scholar 

  • LabuschagnĂ© M, Albertyn J (2007) Cloning of an epoxide hydrolase encoding gene from Rhodotorula mucilaginosa and functional expression in Yarrowia lipolytica. Yeast 24:69–78

    Article  PubMed  CAS  Google Scholar 

  • LabuschagnĂ© M, Botes AL, Albertyn J (2004) Cloning and sequencing of an epoxide hydrolase gene from Rhodosporidium paludigenum. DNA Seq 15:202–205

    PubMed  Google Scholar 

  • Laloi M, Mac Carthy J, Morandi O, Gysler C, Bucheli P (2002) Molecular and biochemical characterisation of two aspartic proteinases TcAP1 and TcAP2 from Theobroma cacao seeds. Planta 215:754–762

    Article  PubMed  CAS  Google Scholar 

  • Le Dall MT, Nicaud JM, Gaillardin C (1994) Multiple-copy integration in the yeast Yarrowia lipolytica. Curr Genet 26:38–44

    Article  PubMed  Google Scholar 

  • Li J, Woo NY (2003) Pathogenicity of Vibrios in fish: an overview. J Ocean Univ Qingdao 2:117–128

    Google Scholar 

  • Li Y, Liu GL, Wang K, Chi ZM, Madzak C (2012) Overexpression of the endo-inulinase gene from Arthrobacter sp. S37 in Yarrowia lipolytica and characterization of the recombinant endo-inulinase. J Mol Catal B Enzym 74(1–2):109–115

    Article  CAS  Google Scholar 

  • Liu G, Yue L, Chi Z, Yu W, Chi Z, Madzak C (2009) The surface display of the alginate lyase on the cells of Yarrowia lipolytica for hydrolysis of alginate. Mar Biotechnol 11:619–626

    Article  PubMed  CAS  Google Scholar 

  • Liu XY, Chi Z, Liu GL, Wang F, Madzak C, Chi ZM (2010) Inulin hydrolysis and citric acid production from inulin using the surface-engineered Yarrowia lipolytica displaying inulinase. Metab Eng 12(5):469–476

    Article  PubMed  CAS  Google Scholar 

  • Madzak C, Blanchin-Roland S, Gaillardin C (1996) Upstream activating sequences and recombinant promoter sequences functional in Yarrowia and vectors containing them. European Patent Application EP0747484 (A1)

    Google Scholar 

  • Madzak C, Blanchin-Roland S, Cordero Otero R, Gaillardin C (1999) Functional analysis of upstream regulating regions from the Yarrowia lipolytica XPR2 promoter. Microbiology 145:75–87

    Article  PubMed  CAS  Google Scholar 

  • Madzak C, TrĂ©ton B, Blanchin-Roland S (2000) Strong hybrid promoters and integrative expression/secretion vectors for quasi-constitutive expression of heterologous proteins in the yeast Yarrowia lipolytica. J Mol Microbiol Biotechnol 2(2):207–216

    PubMed  CAS  Google Scholar 

  • Madzak C, Gaillardin C, Beckerich JM (2004) Heterologous protein expression and secretion in the non-conventional yeast Yarrowia lipolytica: a review. J Biotechnol 109(1–2):63–81

    Article  PubMed  CAS  Google Scholar 

  • Madzak C, Nicaud JM, Gaillardin C (2005a) Yarrowia lipolytica. In: Gellissen G (ed) Production of recombinant proteins: microbial and eucaryotic expression systems. Wiley-VCH, Weinheim, pp 163–189

    Chapter  Google Scholar 

  • Madzak C, Otterbein L, Chamkha M, Moukha S, Asther M, Gaillardin C, Beckerich JM (2005b) Heterologous production of a laccase from the basidiomycete Pycnoporus cinnabarinus in the dimorphic yeast Yarrowia lipolytica. FEMS Yeast Res 5(6–7):635–646

    Article  PubMed  CAS  Google Scholar 

  • Madzak C, Mimmi MC, Caminade E, Brault A, Baumberger S, Briozzo P, Mougin C, Jolivalt C (2006) Shifting the optimal pH of activity for a laccase from the fungus Trametes versicolor by structure-based mutagenesis. Protein Eng Des Sel 19(2):77–84

    Article  PubMed  CAS  Google Scholar 

  • Maharajh D, Roth R, Lalloo R, Simpson C, Mitra R, Gorgens J, Ramchuran S (2008a) Multi-copy expression and fed-batch production of Rhodotorula araucariae epoxide hydrolase in Yarrowia lipolytica. Appl Microbiol Biotechnol 79:235–244

    Article  PubMed  CAS  Google Scholar 

  • Maharajh D, Lalloo R, Gorgens J (2008b) Effect of an exponential feeding regime on the production of Rhodotorula araucariae epoxide hydrolase in Yarrowia lipolytica. Lett Appl Microbiol 47:520–525

    Article  PubMed  CAS  Google Scholar 

  • Malito E, Coda A, Bilyeu KD, Fraaije MW, Mattevi A (2004) Structures of Michaelis and product complexes of plant cytokinin dehydrogenase: implications for flavoenzyme catalysis. J Mol Biol 341:1237–1249

    Article  PubMed  CAS  Google Scholar 

  • Massonneau A, Houba-HĂ©rin N, Pethe C, Madzak C, Falque M, Mercy M, Kopecny D, Majira A, Rogowsky P, Laloue M (2004) Maize cytokinin oxidase genes: differential expression and cloning of two new cDNAs. J Exp Bot 55(408):2549–2557

    Article  PubMed  CAS  Google Scholar 

  • Matoba S, Fukayama J, Wing RA, Ogrydziak DM (1988) Intracellular precursors and secretion of alkaline extracellular protease of Yarrowia lipolytica. Mol Cell Biol 8(11):4904–4916

    PubMed  CAS  Google Scholar 

  • Matsuoka M, Matsubara M, Daidoh H, Imanaka T, Uchida K, Aiba S (1993) Analysis of regions essential for the function of chromosomal replicator sequences from Yarrowia lipolytica. Mol Gen Genet 237:327–333

    PubMed  CAS  Google Scholar 

  • Mayer AM, Staples RC (2002) Laccase: new functions for an old enzyme. Phytochemistry 60(6):551–565

    Article  PubMed  CAS  Google Scholar 

  • Mekouar M, Blanc-Lenfle I, Ozanne C, Da Silva C, Cruaud C, Wincker P, Gaillardin C, NeuvĂ©glise C (2010) Detection and analysis of alternative splicing in Yarrowia lipolytica reveal structural constraints facilitating nonsense-mediated decay of intron-retaining transcripts. Genome Biol 11(6):R65

    Article  PubMed  CAS  Google Scholar 

  • Menendez JA, Vellon L, Colomer R, Lupu R (2005) Effect of gamma-linolenic acid on the transcriptional activity of the Her-2/neu (erbB-2) oncogene. J Natl Cancer Inst 97(21):1611–1615

    Article  PubMed  CAS  Google Scholar 

  • Mougin C, Jolivalt C, Briozzo P, Madzak C (2003) Fungal laccases: from structure-activity studies to environmental applications. Environ Chem Lett 1:145–148

    Article  CAS  Google Scholar 

  • Muesch A, Hartmann E, Rohde K, Rubartelli A, Sitia R, Rapoport TA (1990) A novel pathway for secretory proteins? Trends Biochem Sci 15(3):86–88

    Article  PubMed  CAS  Google Scholar 

  • Muller S, Sandal T, Kamp-Hansen P, Dalboge H (1998) Comparison of expression systems in the yeasts Saccharomyces cerevisiae, Hansenula polymorpha, Kluyveromyces lactis, Schizosaccharomyces pombe and Yarrowia lipolytica. Cloning of two novel promoters from Yarrowia lipolytica. Yeast 14:1267–1283

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa S, Niimura Y, Gojobori T, Tanaka H, Miura K (2008) Diversity of preferred nucleotide sequences around the translation initiation codon in eukaryote genomes. Nucleic Acids Res 36(3):861–871

    Article  PubMed  CAS  Google Scholar 

  • Nakajima T, Ballou CE (1975) Yeast manno-protein biosynthesis: solubilization and selective assay of four mannosyltransferases. Proc Natl Acad Sci USA 72:3912–3916

    Article  PubMed  CAS  Google Scholar 

  • Ni X, Chi Z, Ma C, Madzak C (2008) Cloning, characterization, and expression of the gene encoding alkaline protease in the marine yeast Aureobasidium pullulans 10. Mar Biotechnol 10(3):319–327

    Article  PubMed  CAS  Google Scholar 

  • Ni X, Yue L, Chi Z, Li J, Wang X, Madzak C (2009) Alkaline protease gene cloning from the marine yeast Aureobasidium pullulans HN2-3 and the protease surface display on Yarrowia lipolytica for bioactive peptide production. Mar Biotechnol 11:81–89

    Article  PubMed  CAS  Google Scholar 

  • Nicaud JM, Fabre E, Gaillardin C (1989) Expression of invertase activity in Yarrowia lipolytica and its use as a selective marker. Curr Genet 16:253–260

    Article  PubMed  CAS  Google Scholar 

  • Nicaud JM, Fournier P, La Bonnardiere C, Chasles M, Gaillardin C (1991) Use of ars18 based vectors to increase protein production in Yarrowia lipolytica. J Biotechnol 19:259–270

    Article  PubMed  CAS  Google Scholar 

  • Nicaud JM, Gaillardin C, Seman M, Pignède G (2000) ProcĂ©dĂ© de transformation non-homologue de Yarrowia lipolytica. French Patent Application FR2782733 (A1)

    Google Scholar 

  • Nicaud JM, Madzak C, van den Broek P, Gysler C, Duboc P, Niederberger P, Gaillardin C (2002) Protein expression and secretion in the yeast Yarrowia lipolytica. FEMS Yeast Res 2:371–379

    PubMed  CAS  Google Scholar 

  • Nicaud JM, Fudalej F, NeuvĂ©glise C, Beckerich JM (2009) ProcĂ©dĂ© d’intĂ©gration ciblĂ©e de multicopies d’un gène d’intĂ©rĂŞt dans une souche de Yarrowia. French Patent Application FR2927089 (A1)

    Google Scholar 

  • Nicaud JM, Chardot T, Beopoulos A (2010) New mutant yeast strains capable of accumulating a large quantity of lipids. World Patent Application WO2010004141 (A2)

    Google Scholar 

  • Niu DK, Yang YF (2011) Why eukaryotic cells use introns to enhance gene expression: splicing reduces transcription-associated mutagenesis by inhibiting topoisomerase I cutting activity. Biol Direct 6:24

    Article  PubMed  CAS  Google Scholar 

  • Nthangeni MB, Urban P, Pompon D, Smit MS, Nicaud JM (2004) The use of Yarrowia lipolytica for the expression of human cytochrome P450 CYP1A1. Yeast 21(7):583–592

    Article  PubMed  CAS  Google Scholar 

  • Ogrydziak DM, Scharf SJ (1982) Alkaline extracellular protease produced by Saccharomycopsis lipolytica CX161-1B. J Gen Microbiol 128:1225–1234

    PubMed  CAS  Google Scholar 

  • Ogrydziak DM, Demain AL, Tannenbaum SR (1977) Regulation of extracellular protease production in Candida lipolytica. Biochim Biophys Acta 497:525–538

    Article  PubMed  CAS  Google Scholar 

  • Oh DB, Park JS, Kim MW, Cheon SA, Kim EJ, Moon HY, Kwon O, Rhee SK, Kang HA (2008) Glycoengineering of the methylotrophic yeast Hansenula polymorpha for the production of glycoproteins with trimannosyl core N-glycan by blocking core oligosaccharide assembly. Biotechnol J 3(5):659–668

    Article  PubMed  CAS  Google Scholar 

  • Otterbein L, Record E, Longhi S, Asther M, Moukha S (2000) Molecular cloning of the cDNA encoding laccase from Pycnoporus cinnabarinus I-937 and expression in Pichia pastoris. Eur J Biochem 267:1619–1625

    Article  PubMed  CAS  Google Scholar 

  • Papanikolaou S, Komaitis M, Aggelis G (2004) Single cell oil (SCO) production by Mortierella isabellina grown on high-sugar content media. Bioresour Technol 95:287–291

    Article  PubMed  CAS  Google Scholar 

  • Park CS, Chang CC, Kim JY, Ogrydziak DM, Ryu DDY (1997) Expression, secretion and processing of rice α-amylase in the yeast Yarrowia lipolytica. J Biol Chem 272:6876–6881

    Article  PubMed  CAS  Google Scholar 

  • Park CS, Chang CC, Ryu DDY (2000) Expression and high-level secretion of Trichoderma reesei endoglucanase I in Yarrowia lipolytica. Appl Biochem Biotechnol 87(1):1–15

    Article  PubMed  CAS  Google Scholar 

  • Park JN, Song Y, Kim JY, Oh DB, Kang HA (2008) A novel YlMPO1 gene derived from Yarrowia lipolytica and a process for preparing a glycoprotein not being mannosylphosphorylated by using a mutated Yarrowia lipolytica in which YlMPO1 gene is disrupted. World Patent Application WO2008136564 (A1)

    Google Scholar 

  • Park JN, Song Y, Cheon SA, Kwon O, Oh DB, Jigami Y, Kim JY, Kang HA (2011) Essential role of YlMPO1, a novel Yarrowia lipolytica homologue of Saccharomyces cerevisiae MNN4, in mannosylphosphorylation of N- and O-linked glycans. Appl Environ Microbiol 77(4):1187–1195

    Article  PubMed  CAS  Google Scholar 

  • Paulick MG, Bertozzi CR (2008) The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins. Biochemistry 47(27):6991–7000

    Article  PubMed  CAS  Google Scholar 

  • Peng Y, Liu GL, Yu XJ, Wang XH, Jing L, Chi ZM (2011) Cloning of exo-β-1,3-glucanase gene from a marine yeast Williopsis saturnus and its overexpression in Yarrowia lipolytica. Mar Biotechnol (NY) 13(2):193–204

    Article  CAS  Google Scholar 

  • Pepper LR, Cho YK, Boder ET, Shusta EV (2008) A decade of yeast surface display technology: where are we now? Comb Chem High Throughput Screen 11(2):127–134

    Article  PubMed  CAS  Google Scholar 

  • Picataggio SK, Zhu Q (2005) Glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate mutase promoters for gene expression in oleaginous yeast. World Patent Application WO2005003310 (A2)

    Google Scholar 

  • Pignède G, Wang H, Fudalej F, Seman M, Gaillardin C, Nicaud JM (2000) Autocloning and amplification of LIP2 in Yarrowia lipolytica. Appl Environ Microbiol 66(8):3283–3289

    Article  PubMed  Google Scholar 

  • Poirier Y, Erard N, PetĂ©tot JM (2001) Synthesis of polyhydroxyalkanoate in the peroxisome of Saccharomyces cerevisiae by using intermediates of fatty acid beta-oxidation. Appl Environ Microbiol 67(11):5254–5260

    Article  PubMed  CAS  Google Scholar 

  • Pollak DM, Zhu Q (2005) Fructose biphosphate aldolase regulatory sequences for gene expression in oleaginous yeast. World Patent Application WO2005049805 (A2)

    Google Scholar 

  • Rao A, Pimprikar P, Bendigiri C, Kumar AR, Zinjarde S (2011) Cloning and expression of a tyrosinase from Aspergillus oryzae in Yarrowia lipolytica: application in L-DOPA biotransformation. Appl Microbiol Biotechnol 92(5):951–959

    Article  PubMed  CAS  Google Scholar 

  • Record E, Punt PJ, Chamkha M, Labat M, van den Hondel CA, Asther M (2002) Expression of the Pycnoporus cinnabarinus laccase gene in Aspergillus niger and characterization of the recombinant enzyme. Eur J Biochem 269(2):602–609

    Article  PubMed  CAS  Google Scholar 

  • Richard M, Quijano RR, Bezzate S, Bordon-Pallier F, Gaillardin C (2001) Tagging morphogenetic genes by insertional mutagenesis in the yeast Yarrowia lipolytica. J Bacteriol 183(10):3098–3107

    Article  PubMed  CAS  Google Scholar 

  • Romanos MA, Scorer CA, Clare JJ (1992) Foreign gene expression in yeast: a review. Yeast 8:423–488

    Article  PubMed  CAS  Google Scholar 

  • Roth R, Moodley V, van Zyl P (2009) Heterologous expression and optimized production of an Aspergillus aculeatus endo-1,4-beta-mannanase in Yarrowia lipolytica. Mol Biotechnol 43(2):112–120

    Article  PubMed  CAS  Google Scholar 

  • Rothblatt JA, Meyer DI (1986) Secretion in yeast: translocation and glycosylation of prepro-alpha-factor in vitro can occur via an ATP-dependent post-translational mechanism. EMBO J 5(5):1031–1036

    PubMed  CAS  Google Scholar 

  • Ruiz-Herrera J, Sentandreu R (2002) Different effectors of dimorphism in Yarrowia lipolytica. Arch Microbiol 178(6):477–483

    Article  PubMed  CAS  Google Scholar 

  • Schmid-Berger N, Schmid B, Barth G (1994) Ylt1, a highly repetitive retrotransposon in the genome of the dimorphic fungus Yarrowia lipolytica. J Bacteriol 176:2477–2482

    PubMed  CAS  Google Scholar 

  • Setati ME, Ademark P, van Zyl WH, Hahn-Hägerdal B, StĂĄlbrand H (2001) Expression of the Aspergillus aculeatus endo-beta-1,4-mannanase encoding gene (man1) in Saccharomyces cerevisiae and characterization of the recombinant enzyme. Protein Expr Purif 21(1):105–114

    Article  PubMed  CAS  Google Scholar 

  • Sharpe P, Ye R, Zhu Q (2008) Production de carotĂ©noĂŻdes dans une levure olĂ©agineuse recombinante. World Patent Application WO2008073367 (A1)

    Google Scholar 

  • Shibasaki S, Maeda H, Ueda M (2009) Molecular display technology using yeast-arming technology. Anal Sci 25(1):41–49

    Article  PubMed  CAS  Google Scholar 

  • Shiningavamwe A, Obiero G, Albertyn J, Nicaud JM, Smit M (2006) Heterologous expression of the benzoate para-hydroxylase encoding gene (CYP53B1) from Rhodotorula minuta in Yarrowia lipolytica. Appl Microbiol Biotechnol 72(2):323–329

    Article  PubMed  CAS  Google Scholar 

  • Shusta EV, Raines RT, PlĂĽckthun A, Wittrup KD (1998) Increasing the secretory capacity of Saccharomyces cerevisiae for production of single-chain antibody fragments. Nat Biotechnol 16(8):773–777

    Article  PubMed  CAS  Google Scholar 

  • Sohn YS, Park CS, Lee SB, Ryu DD (1998) Disruption of PMR1, encoding a Ca2+-ATPase homolog in Yarrowia lipolytica, affects secretion and processing of homologous and heterologous proteins. J Bacteriol 180(24):6736–6742

    PubMed  CAS  Google Scholar 

  • Song Y, Choi MH, Park JN, Kim MW, Kim EJ, Kang HA, Kim JY (2007) Engineering of the yeast Yarrowia lipolytica for the production of glycoproteins lacking the outer-chain mannose residues of N-glycans. Appl Environ Microbiol 73(14):4446–4454

    Article  PubMed  CAS  Google Scholar 

  • Song H, Zhou L, Zhang L, Gao B, Wei D, Shen Y, Wang R, Madzak C, Jiang Z (2011) Construction of a whole-cell catalyst displaying a fungal lipase for effective treatment of oily wastewaters. J Mol Catal B Enzym 71:166–170

    Article  CAS  Google Scholar 

  • Steinborn G, Böer E, Scholz A, Tag K, Kunze G, Gellissen G (2006) Application of a wide-range yeast vector (CoMed) system to recombinant protein production in dimorphic Arxula adeninivorans, methylotrophic Hansenula polymorpha and other yeasts. Microb Cell Fact 5:33–45

    Article  PubMed  CAS  Google Scholar 

  • Swennen D, Beckerich JM (2007) Yarrowia lipolytica vesicle-mediated protein transport pathways. BMC Evol Biol 7:219–237

    Article  PubMed  CAS  Google Scholar 

  • Swennen D, Paul MF, Vernis L, Beckerich JM, Fournier A, Gaillardin C (2002) Secretion of active anti-Ras single-chain Fv antibody by the yeasts Yarrowia lipolytica and Kluyveromyces lactis. Microbiology 148:41–50

    PubMed  CAS  Google Scholar 

  • Swennen D, Henry C, Beckerich JM (2010) Folding proteome of Yarrowia lipolytica targeting with uracil permease mutants. J Proteome Res 9(12):6169–6179

    Article  PubMed  CAS  Google Scholar 

  • Tharaud C, Ribet AM, Costes C, Gaillardin C (1992) Secretion of human blood coagulation factor XIIIa by the yeast Yarrowia lipolytica. Gene 121:111–119

    Article  PubMed  CAS  Google Scholar 

  • Thompson A, Gasson MJ (2001) Location effects of a reporter gene on expression levels and on native protein synthesis in Lactococcus lactis and Saccharomyces cerevisiae. Appl Environ Microbiol 67(8):3434–3439

    Article  PubMed  CAS  Google Scholar 

  • Tobe S, Takami T, Ikeda S, Mitsugi K (1976) Production and some enzymatic properties of alkaline protease of Candida lipolytica. Agric Biol Chem 40:1087–1092

    Article  CAS  Google Scholar 

  • Trimble RB, Atkinson PH, Tschopp JF, Townsend RR, Maley F (1991) Structure of oligosaccharide on Saccharomyces SUC2 invertase secreted by the methylotrophic yeast Pichia pastoris. J Biol Chem 266:22807–22817

    PubMed  CAS  Google Scholar 

  • van Uden N, Fell JW (1968) Marine yeasts. Adv Microbiol Sea 1:167–201

    Google Scholar 

  • van Zyl PJ (2010) A method for producing a polypeptide in Yarrowia lipolytica. World Patent Application WO2011148339 (A1)

    Google Scholar 

  • van Zyl PJ, Moodley V, Rose SH, Roth RL, van Zyl WH (2009) Production of the Aspergillus aculeatus endo-1,4-beta-mannanase in A. niger. J Ind Microbiol Biotechnol 36(4):611–617

    Article  PubMed  CAS  Google Scholar 

  • Vernis L, Abbas A, Chasles M, Gaillardin C, Brun C, Huberman JA, Fournier P (1997) An origin of replication and a centromere are both needed to establish a replicative plasmid in the yeast Yarrowia lipolytica. Mol Cell Biol 17:1995–2004

    PubMed  CAS  Google Scholar 

  • Walter P, Blobel G (1980) Purification of a membrane-associated protein complex required for protein translocation across the endoplasmic reticulum. Proc Natl Acad Sci USA 77(12):7112–7116

    Article  PubMed  CAS  Google Scholar 

  • Walter P, Blobel G (1983) Disassembly and reconstitution of signal recognition particle. Cell 34(2):525–533

    Article  PubMed  CAS  Google Scholar 

  • Wang F, Yue L, Wang L, Madzak C, Li J, Wang X, Chi Z (2009) Genetic modification of the marine-derived yeast Yarrowia lipolytica with high-protein content using a GPI-anchor-fusion expression system. Biotechnol Prog 25(5):1297–1303

    Article  PubMed  CAS  Google Scholar 

  • Wang JH, Hung W, Tsai SH (2011) High efficiency transformation by electroporation of Yarrowia lipolytica. J Microbiol 49(3):469–472

    Article  PubMed  Google Scholar 

  • Werck-Reichhart D, Feyereisen R (2000) Cytochromes P450: a success story. Genome Biol 1(6):reviews3003.1–reviews3003.9

    Article  Google Scholar 

  • Werner T, Schmulling T (2009) Cytokinin action in plant development. Curr Opin Plant Biol 12(5):527–538

    Article  PubMed  CAS  Google Scholar 

  • Wojtatowicz M, Rymowicz W, Robak M, Zarowska B, Nicaud JM (1997) Kinetics of cell growth and citric acid production by Yarrowia lipolytica Suc+ transformants in sucrose media. Pol J Food Nutr Sci 6/47(4):49–54

    Google Scholar 

  • Xuan JW, Fournier P, Gaillardin C (1988) Cloning of the LYS5 gene encoding saccharopine dehydrogenase from the yeast Yarrowia lipolytica by target integration. Curr Genet 14:15–21

    Article  CAS  Google Scholar 

  • Xue Z, Zhu Q (2006a) Glycerol-3-phosphate o-acyl transferase promoter for gene expression in oleaginous yeast. World Patent Application WO2006031937 (A2)

    Google Scholar 

  • Xue Z, Zhu Q (2006b) Ammonium transporter promoter for gene expression in oleaginous yeast. World Patent Application WO2006052754 (A2)

    Google Scholar 

  • Xue Z, Yadav N, Zhu Q (2007) Optimized strains of Yarrowia lipolytica for high eicosapentaenoic acid production. European Patent Application EP2195415 (A1)

    Google Scholar 

  • Yang CH, Liu WH (2007) Cloning and characterization of a maltotriose-producing α-amylase gene from Thermobifida fusca. J Ind Microbiol Biotechnol 34(4):325–330

    Article  PubMed  CAS  Google Scholar 

  • Yang XS, Jiang ZB, Song HT, Jiang SJ, Madzak C, Ma LX (2009) Cell-surface display of the active mannanase in Yarrowia lipolytica with a novel surface-display system. Biotechnol Appl Biochem 54(3):171–176

    Article  PubMed  CAS  Google Scholar 

  • Yang CH, Huang YC, Chen CY, Wen CY (2010a) Expression of Thermobifida fusca thermostable raw starch digesting alpha-amylase in Pichia pastoris and its application in raw sago starch hydrolysis. J Ind Microbiol Biotechnol 37(4):401–406

    Article  PubMed  CAS  Google Scholar 

  • Yang CH, Huang YC, Chen CY, Wen CY (2010b) Heterologous expression of Thermobifida fusca thermostable alpha-amylase in Yarrowia lipolytica and its application in boiling stable resistant sago starch preparation. J Ind Microbiol Biotechnol 37(9):953–960

    Article  PubMed  CAS  Google Scholar 

  • Yaver DS, Matoba S, Ogrydziak DM (1992) A mutation in the signal recognition particle 7S RNA of the yeast Yarrowia lipolytica preferentially affects synthesis of the alkaline extracellular protease: in vivo evidence for translational arrest. J Cell Biol 116:605–616

    Article  PubMed  CAS  Google Scholar 

  • Yu XJ, Madzak C, Li HJ, Chi ZM, Li J (2010) Surface display of acid protease on the cells of Yarrowia lipolytica for milk clotting. Appl Microbiol Biotechnol 87(2):669–677

    Article  PubMed  CAS  Google Scholar 

  • Yue L, Chi Z, Wang L, Liu J, Madzak C, Li J, Wang X (2008) Construction of a new plasmid for surface display on cells of Yarrowia lipolytica. J Microbiol Methods 72:116–123

    Article  PubMed  CAS  Google Scholar 

  • Yuzbashev TV, Yuzbasheva EY, Vibornaya TV, Sobolevskaya TI, Laptev IA, Gavrikov AV, Sineoky SP (2012) Production of recombinant Rhizopus oryzae lipase by the yeast Yarrowia lipolytica results in increased enzymatic thermostability. Protein Expr Purif 82:83–89

    Article  PubMed  CAS  Google Scholar 

  • Zhang N, Suen WC, Windsor W, Xiao L, Madison V, Zaks A (2003) Improving tolerance of Candida antarctica lipase B towards irreversible thermal inactivation through directed evolution. Protein Eng 16(8):599–605

    Article  PubMed  CAS  Google Scholar 

  • Zhao CH, Cui W, Liu XY, Chi ZM, Madzak C (2010) Expression of inulinase gene in the oleaginous yeast Yarrowia lipolytica and single cell oil production from inulin-containing materials. Metab Eng 12(6):510–517

    Article  PubMed  CAS  Google Scholar 

  • Zhu KL, Chi ZM, Li J, Zhang FL, Li MJ, Yasoda HN, Wu LF (2006) The surface display of haemolysin from Vibrio harveyi on yeast cells and their potential applications as live vaccine in marine fish. Vaccine 24:6046–6052

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We wish to thank all colleagues and collaborators who accepted to communicate unpublished data: Dr. Martine Chartier (Laboratoire d’Ingénierie des Systèmes Macromoléculaires, CNRS, Marseille, France), Prof. Zhen-Ming Chi (Unesco Chinese Center of Marine Biotechnology and Institute of Marine Biodiversity and Evolution, Ocean University of China, Qingdao, China), Dr. Ricardo Cordero (former PhD student from our laboratory), Dr. Art Franke (Pfizer, USA), Dr. Christof Gysler (Nestec, Switzerland), Dr. Nicole Houba-Hérin (Laboratoire de Biologie Cellulaire, INRA, Versailles, France), Dr. Claude Jolivalt (ENSCP Chimie ParisTech, Laboratoire Charles Friedel, Paris, France), Dr. Gotthard Kunze (Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung, Gatersleben, Germany), Dr. Nathalie Libessart (Roquette Frères, France), Dr. Bi-Ching Sang (Pharmingen, USA), Dr. Dominique Swennen (our laboratory), Dr. Kohji Uchida (Oriental Yeast, Japan) and Dr. Petrus J. van Zyl (Bioprocess Development, CSIR Biosciences, Modderfontein, South Africa).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Catherine Madzak .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Madzak, C., Beckerich, JM. (2013). Heterologous Protein Expression and Secretion in Yarrowia lipolytica . In: Barth, G. (eds) Yarrowia lipolytica. Microbiology Monographs, vol 25. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38583-4_1

Download citation

Publish with us

Policies and ethics