A set of aspartyl protease-deficient strains for improved expression of heterologous proteins in Kluyveromyces lactis

FEMS Yeast Research

Volumn 11, Issue 2, 2011, Pages 168-178

  Ganatra, Mehul B ^a   Vainauskas, Saulius ^a   Hong, Julia M ^a   Taylor, Troy E ^b   Denson, John Paul M ^b   Esposito, Dominic ^b   Read, Jeremiah D ^a   Schmeisser, Hana ^c   Zoon, Kathryn C ^c   Hartley, James L ^b   Taron, Christopher H ^a  

^a Division of Gene Expression   (United States)

^b SAIC FREDERICK INC   (United States)

^c NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

Aspartic protease; Kluyveromyces lactis; Protein degradation; Protein expression; Yapsin

Indexed keywords

ASPARTIC PROTEINASE; HUMAN INTERFERON; LUCIFERASE;

ARTICLE; ASPERGILLUS NIDULANS; BACTERIAL STRAIN; CONTROLLED STUDY; DELETION MUTANT; ENZYME ACTIVITY; GENOME; KLUYVEROMYCES LACTIS; NONHUMAN; POLYMERASE CHAIN REACTION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; WILD TYPE;

ARECACEAE; ASPARTIC ACID PROTEASES; DNA, FUNGAL; FUNGAL PROTEINS; GENE DELETION; GENE EXPRESSION; KLUYVEROMYCES; LUCIFERASES; MOLECULAR SEQUENCE DATA; MUTAGENESIS; RECOMBINANT PROTEINS; SEQUENCE ANALYSIS, DNA;

EMERICELLA NIDULANS; GAUSSIA PRINCEPS (T. SCOTT, 1894); KLUYVEROMYCES LACTIS;

EID: 79951498720     PISSN: 15671356     EISSN: 15671364     Source Type: Journal    
DOI: 10.1111/j.1567-1364.2010.00703.x     Document Type: Article

References (40)

1. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W & Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25: 3389-3402.
2. Aoki S, Ito-Kuwa S, Nakamura K, Kato J, Ninomiya K & Vidotto V (1994) Extracellular proteolytic activity of Cryptococcus neoformans. Mycophatologia 128: 143-150.
3. Ballensiefen W & Schmitt HD (1997) Periplasmic Bar1 protease of Saccharomyces cerevisiae is active before reaching its extracellular destination. Eur J Biochem 247: 142-147.
4. Bendtsen JD, Nielsen H, von Heijne G & Brunak S (2004) Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340: 783-795.
5. Bourbonnais Y, Larouche C & Tremblay GM (2000) Production of full-length human pre-elafin, an elastase specific inhibitor, from yeast requires the absence of a functional yapsin 1 (Yps1p) endoprotease. Protein Expres Purif 20: 485-491.
6. Chan RK & Otte CA (1982) Physiological characterization of Saccharomyces cerevisiae mutants supersensitive to G1 arrest by a factor and alpha factor pheromones. Mol Cell Biol 2: 21-29.
7. Colussi PA & Taron CH (2005) Kluyveromyces lactis LAC4 promoter variants that lack function in bacteria but retain full function in yeast. Appl Environ Microb 71: 7092-7098.
8. Copley KS, Alm SM, Schooley DA & Courchesne WE (1998) Expression, processing and secretion of a proteolytically-sensitive insect diuretic hormone by Saccharomyces cerevisiae requires the use of a yeast strain lacking genes encoding the Yap3 and Mkc7 endoproteases found in the secretory pathway. Biochem J 330: 1333-1340.
9. Egel-Mitani M, Flygenring HP & Hansen MT (1990) A novel aspartyl protease allowing KEX2-independent MF alpha propheromone processing in yeast. Yeast 6: 127-137.
10. Egel-Mitani M, Andersen AS, Diers II, Hach M, Thim L, Hastrup S & Vad K (2000) Yield improvement of heterologous peptides expressed in yps1-disrupted Saccharomyces cerevisiae strains. Enzyme Microb Tech 26: 671-677.
11. Eisenhaber B, Bork P & Eisenhaber F (1999) Prediction of potential GPI-modification sites in proprotein sequences. J Mol Biol 292: 741-758.
12. Esposito D, Gillette WK, Miller DA et al. (2005) Gateway cloning is compatible with protein secretion from Pichia pastoris. Protein Expres Purif 40: 424-428.
13. Görgens JF, Planas J, van Zyl WH, Knoetze JH & Hahn-Hägerdal B (2004) Comparison of three expression systems for heterologous xylanase production by S. cerevisiae in defined medium. Yeast 21: 1205-1217.
14. Hu R, Bekisz J, Hayes M, Audet S, Beeler J, Petricoin E & Zoon K (1999) Divergence of binding, signaling, and biological responses to recombinant human hybrid IFN. J Immunol 163: 854-860.
15. Kang HA, Kim SJ, Choi ES, Rhee SK & Chung BH (1998) Efficient production of intact human parathyroid hormone in a Saccharomyces cerevisiae mutant deficient in yeast aspartic protease 3 (YAP3). Appl Microbiol Biot 50: 187-192.
16. Kaur R, Ma B & Cormack BP (2007) A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata. P Natl Acad Sci USA 104: 7628-7633.
17. Kerry-Williams SM, Gilbert SC, Evans LR & Ballance DJ (1998) Disruption of the Saccharomyces cerevisiae YAP3 gene reduces the proteolytic degradation of secreted recombinant human albumin. Yeast 14: 161-169.
18. Komano H, Rockwell N, Wang GT, Krafft GA & Fuller RS (1999) Purification and characterization of the yeast glycosylphosphatidylinositol-anchored, monobasic-specific aspartyl protease yapsin 2 (Mkc7p). J Biol Chem 274: 24431-24437.
19. Kopecká M & Gabriel M (1992) The influence of Congo red on the cell wall and (1→3)-β-d-glucan microfibril biogenesis in Saccharomyces cerevisiae. Arch Microbiol 158: 115-126.
20. Krysan DJ, Ting EL, Abeijon C, Kroos L & Fuller RS (2005) Yapsins are a family of aspartyl proteases required for cell wall integrity in Saccharomyces cerevisiae. Eukaryot Cell 4: 1364-1374.
21. MacKay VL, Welch SK, Insley MY, Manney TR, Holly J, Saari GC & Parker ML (1988) The Saccharomyces cerevisiaeBAR1 gene encodes an exported protein with homology to pepsin. P Natl Acad Sci USA 85: 55-59.
22. Madinger CL, Sharma SS, Anton BP, Fields LG, Cushing ML, Canovas J, Taron CH & Benner JS (2009) The effect of carbon source on the secretome of Kluyveromyces lactis. Proteomics 9: 4744-4754.
23. Marques M, Mojzita D, Amorim MA, Almeida T, Hohmann S, Moradas-Ferreira P & Costa V (2006) The Pep4p vacuolar proteinase contributes to the turnover of oxidized proteins but PEP4 overexpression is not sufficient to increase chronological lifespan in Saccharomyces cerevisiae. Microbiology 152: 3595-3605.
24. Ogrydziak DM (1993) Yeast extracellular proteases. Crit Rev Biotechnol 13: 1-55.
25. Olsen V, Cawley NX, Brandt J, Egel-Mitani M & Loh YP (1999) Identification and characterization of Saccharomyces cerevisiae yapsin 3, a new member of the yapsin family of aspartic proteases encoded by the YPS3 gene. Biochem J 339: 407-411.
26. Ram AF, Wolters A, Ten Hoopen R & Klis FM (1994) A new approach for isolating cell wall mutants in Saccharomyces cerevisiae by screening for hypersensitivity to calcofluor white. Yeast 10: 1019-1030.
27. Ray MK, Devi KU, Kumar GS & Shivaji S (1992) Extracellular protease from the antarctic yeast Candida humicola. Appl Environ Microb 58: 1918-1923.
28. Read JD, Colussi PA, Ganatra MB & Taron CH (2007) Acetamide selection of Kluyveromyces lactis cells transformed with an integrative vector leads to high-frequency formation of multicopy strains. Appl Environ Microb 73: 5088-5096.
29. Rourke IJ, Johnsen AH, Din N, Petersen JG & Rehfeld JF (1997) Heterologous expression of human cholecystokinin in Saccharomyces cerevisiae. Evidence for a lysine-specific endopeptidase in the yeast secretory pathway. J Biol Chem 272: 9720-9727.
30. Rozan L, Krysan DJ, Rockwell NC & Fuller RS (2004) Plasticity of extended subsites facilitates divergent substrate recognition by Kex2 and furin. J Biol Chem 279: 35656-35663.
31. Rupp S & Wolf DH (1995) Biogenesis of the yeast vacuole (lysosome). The use of active-site mutants of proteinase yscA to determine the necessity of the enzyme for vacuolar proteinase maturation and proteinase yscB stability. Eur J Biochem 231: 115-125.
32. Selten GCM, Swinkels BW & Van Gorcom RFM (1999) Selection marker gene free recombinant strains: method for obtaining them and the use of these strains, U.S. Patent 5, 876, 988.
33. Sinha J, Plantz BA, Inan M & Meagher MM (2004) Causes of proteolytic degradation of secreted recombinant proteins produced in methylotrophic yeast Pichia pastoris: case study with recombinant ovine interferon-tau. Biotechnol Bioeng 89: 102-112.
34. Swaim CL, Anton BP, Sharma SS, Taron CH & Benner JS (2008) Physical and computational analysis of the yeast Kluyveromyces lactis secreted proteome. Proteomics 8: 2714-2723.
35. van den Berg JA, van der Laken KJ, van Ooyen AJ et al. (1990) Kluyveromyces as a host for heterologous gene expression: expression and secretion of prochymosin. Biotechnology (NY) 8: 135-139.
36. van Ooyen AJJ, Dekker P, Huang M, Olsthoorn MMA, Jacobs DI, Colussi PA & Taron CH (2006) Heterologous protein production in the yeast Kluyveromyces lactis. FEMS Yeast Res 6: 381-392.
37. Verhaegent M & Christopoulos TK (2002) Recombinant Gaussia luciferase. Overexpression, purification, and analytical application of a bioluminescent reporter for DNA hybridization. Anal Chem 74: 4378-4385.
38. Werten MW & de Wolf FA (2005) Reduced proteolysis of secreted gelatin and Yps1-mediated alpha-factor leader processing in a Pichia pastoris kex2 disruptant. Appl Environ Microb 71: 2310-2317.
39. Woolford CA, Daniels LB, Park FJ, Jones EW, Van Arsdell JN & Innis MA (1986) The PEP4 gene encodes an aspartyl protease implicated in the posttranslational regulation of Saccharomyces cerevisiae vacuolar hydrolases. Mol Cell Biol 6: 2500-2510.
40. Yao XQ, Zhao HL, Xue C, Zhang W, Xiong XH, Wang ZW, Li XY & Liu ZM (2009) Degradation of HSA-AX15(R13K) when expressed in Pichia pastoris can be reduced via the disruption of YPS1 gene in this yeast. J Biotechnol 139: 131-136.