Enhanced Production of Recombinant Secretory Proteins in Pichia pastoris by Optimizing Kex2 P1' site

PLoS ONE

Volumn 8, Issue 9, 2013, Pages

  Yang, Song ^a   Kuang, Ye ^a,b   Li, Hongbo ^a,c   Liu, Yuehong ^a,b   Hui, Xiaoyan ^d   Li, Peng ^a   Jiang, Zhiwu ^a   Zhou, Yulai ^b   Wang, Yu ^a,d   Xu, Aimin ^a,d   Li, Shiwu ^e   Liu, Pentao ^f   Wu, Donghai ^a  

^a GUANGZHOU INSTITUTES OF BIOMEDICINE AND HEALTH   (China)

^b JILIN UNIVERSITY   (China)

^c HUAIHUA UNIVERSITY   (China)

^d UNIVERSITY OF HONG KONG   (Hong Kong)

^e UNIVERSITY OF FLORIDA   (United States)

^f WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

RECOMBINANT PROTEIN; SECRETORY PROTEIN;

AMINO ACID ANALYSIS; ARTICLE; CONTROLLED STUDY; EXPRESSION VECTOR; FLUORESCENCE ANALYSIS; FUNGAL GENOME; GENE DOSAGE; GENE FUNCTION; GENE STRUCTURE; KEX2 GENE; LUMINESCENCE; NONHUMAN; PICHIA PASTORIS; PROCESS OPTIMIZATION; PROTEIN EXPRESSION; PROTEIN SECRETION; PROTEIN SYNTHESIS;

PICHIA; PICHIA PASTORIS;

FUNGAL PROTEINS; GENE EXPRESSION; GENE ORDER; GENETIC VECTORS; LUMINESCENT MEASUREMENTS; PICHIA; PROPROTEIN CONVERTASES; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN TRANSPORT; RECOMBINANT PROTEINS; TRANSFORMATION, GENETIC;

EID: 84884379098     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0075347     Document Type: Article

References (54)

1. Goodman M, (2009) Market watch: Sales of biologics to show robust growth through to 2013. Nat Rev Drug Discov 8: 837. doi:10.1038/nrd3040. PubMed: 19876035.
2. Sheridan C, (2010) Fresh from the biologic pipeline-2009. Nat Biotechnol 28: 307-310. doi:10.1038/nbt0410-307. PubMed: 20379168.
3. Macauley-Patrick S, Fazenda ML, McNeil B, Harvey LM, (2005) Heterologous protein production using the Pichia pastoris expression system. Yeast 22: 249-270. doi:10.1002/yea.1208. PubMed: 15704221.
4. Li P, Anumanthan A, Gao XG, Ilangovan K, Suzara VV, et al. (2007) Expression of recombinant proteins in Pichia pastoris. Appl Biochem Biotechnol 142: 105-124. doi:10.1007/s12010-007-0003-x. PubMed: 18025573.
5. Cos O, Ramón R, Montesinos JL, Valero F, (2006) Operational strategies, monitoring and control of heterologous protein production in the methylotrophic yeast Pichia pastoris under different promoters: a review. Microb Cell Factories 5: 17. doi:10.1186/1475-2859-5-S1-S17. PubMed: 16600031.
6. Cereghino GP, 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. doi:10.1016/S0958-1669(02)00330-0. PubMed: 12323354.
7. Rosenfeld SA, (1999) Use of Pichia pastoris for expression of recombinant proteins. Methods Enzymol 306: 154-169. doi:10.1016/S0076-6879(99)06011-5. PubMed: 10432453.
8. Romanos M, (1995) Advances in the use of Pichia pastoris for high-level gene expression. Curr Opin Biotechnol 6: 527-533. doi:10.1016/0958-1669(95)80087-5.
9. Stadlmayr G, Benakovitsch K, Gasser B, Mattanovich D, Sauer M, (2010) Genome-scale analysis of library sorting (GALibSo): Isolation of secretion enhancing factors for recombinant protein production in Pichia pastoris. Biotechnol Bioeng 105: 543-555. doi:10.1002/bit.22573. PubMed: 19816964.
10. Mattanovich D, Graf A, Stadlmann J, Dragosits M, Redl A, et al. (2009) Genome, secretome and glucose transport highlight unique features of the protein production host Pichia pastoris. Microb Cell Factories 8: 29. doi:10.1186/1475-2859-8-29. PubMed: 19490607.
11. De Schutter K, Lin YC, Tiels P, Van Hecke A, Glinka S, et al. (2009) Genome sequence of the recombinant protein production host Pichia pastoris. Nat Biotechnol 27: 561-566. doi:10.1038/nbt.1544. PubMed: 19465926.
12. Graf A, Gasser B, Dragosits M, Sauer M, Leparc GG, et al. (2008) Novel insights into the unfolded protein response using Pichia pastoris specific DNA microarrays. BMC Genomics 9: 390. doi:10.1186/1471-2164-9-390. PubMed: 18713468.
13. Resina D, Bollók M, Khatri NK, Valero F, Neubauer P, et al. (2007) Transcriptional response of P. pastoris in fed-batch cultivations to Rhizopus oryzae lipase production reveals UPR induction. Microb Cell Factories 6: 21. doi:10.1186/1475-2859-6-21. PubMed: 17634115.
14. Gasser B, Sauer M, Maurer M, Stadlmayr G, Mattanovich D, (2007) Transcriptomics-based identification of novel factors enhancing heterologous protein secretion in yeasts. Appl Environ Microbiol 73: 6499-6507. doi:10.1128/AEM.01196-07. PubMed: 17766460.
15. Gasser B, Maurer M, Rautio J, Sauer M, Bhattacharyya A, et al. (2007) Monitoring of transcriptional regulation in Pichia pastoris under protein production conditions. BMC Genomics 8: 179. doi:10.1186/1471-2164-8-179. PubMed: 17578563.
16. Dragosits M, Stadlmann J, Albiol J, Baumann K, Maurer M, et al. (2009) The effect of temperature on the proteome of recombinant Pichia pastoris. J Proteome Res 8: 1380-1392. doi:10.1021/pr8007623. PubMed: 19216534.
17. Jacobs PP, Geysens S, Vervecken W, Contreras R, Callewaert N, (2009) Engineering complex-type N-glycosylation in Pichia pastoris using GlycoSwitch technology. Nat Protoc 4: 58-70. PubMed: 19131957.
18. Stadheim TA, Li H, Kett W, Burnina IN, Gerngross TU, (2008) Use of high-performance anion exchange chromatography with pulsed amperometric detection for O-glycan determination in yeast. Nat Protoc 3: 1026-1031. doi:10.1038/nprot.2008.76. PubMed: 18546597.
19. Li H, Sethuraman N, Stadheim TA, Zha D, Prinz B, et al. (2006) Optimization of humanized IgGs in glycoengineered Pichia pastoris. Nat Biotechnol 24: 210-215. doi:10.1038/nbt1178. PubMed: 16429149.
20. Xuan Y, Zhou X, Zhang W, Zhang X, Song Z, et al. (2009) An upstream activation sequence controls the expression of AOX1 gene in Pichia pastoris. FEMS Yeast Res 9: 1271-1282. doi:10.1111/j.1567-1364.2009.00571.x. PubMed: 19788557.
21. Hartner FS, Ruth C, Langenegger D, Johnson SN, Hyka P, et al. (2008) Promoter library designed for fine-tuned gene expression in Pichia pastoris. Nucleic Acids Res 36: e76. doi:10.1093/nar/gkn369. PubMed: 18539608.
22. Guerfal M, Ryckaert S, Jacobs PP, Ameloot P, Van Craenenbroeck K, et al. (2010) The HAC1 gene from Pichia pastoris: characterization and effect of its overexpression on the production of secreted, surface displayed and membrane proteins. Microb Cell Factories 9: 49. doi:10.1186/1475-2859-9-49. PubMed: 20591165.
23. Inan M, Aryasomayajula D, Sinha J, Meagher MM, (2006) Enhancement of protein secretion in Pichia pastoris by overexpression of protein disulfide isomerase. Biotechnol Bioeng 93: 771-778. doi:10.1002/bit.20762. PubMed: 16255058.
24. Gasser B, Maurer M, Gach J, Kunert R, Mattanovich D, (2006) Engineering of Pichia pastoris for improved production of antibody fragments. Biotechnol Bioeng 94: 353-361. doi:10.1002/bit.20851. PubMed: 16570317.
25. Love KR, Politano TJ, Panagiotou V, Jiang B, Stadheim TA, et al. (2012) Systematic Single-Cell Analysis of Pichia pastoris Reveals Secretory Capacity Limits Productivity. PLOS ONE 7: e37915. doi:10.1371/journal.pone.0037915. PubMed: 22685548.
26. Werten MW, van den Bosch TJ, Wind RD, Mooibroek H, de Wolf FA, (1999) High-yield secretion of recombinant gelatins by Pichia pastoris. Yeast 15: 1087-1096. doi:10.1002/(SICI)1097-0061(199908)15:11. PubMed: 10455232.
27. Sumi A, Okuyama K, Kobayashi K, Ohtani W, Ohmura T, et al. (1999) Purification of recombinant human serum albumin efficient purification using STREAMLINE. Bioseparation 8: 195-200. doi:10.1023/A:1008081314112. PubMed: 10734571.
28. Potgieter TI, Cukan M, Drummond JE, Houston-Cummings NR, Jiang Y, et al. (2009) Production of monoclonal antibodies by glycoengineered Pichia pastoris. J Biotechnol 139: 318-325. doi:10.1016/j.jbiotec.2008.12.015. PubMed: 19162096.
29. Fuller RS, Brake AJ, Thorner J, (1989) Intracellular targeting and structural conservation of a prohormone-processing endoprotease. Science 246: 482-486. doi:10.1126/science.2683070. PubMed: 2683070.
30. Fuller RS, Brake A, Thorner J, (1989) Yeast prohormone processing enzyme (KEX2 gene product) is a Ca2+-dependent serine protease. Proc Natl Acad Sci U S A 86: 1434-1438. doi:10.1073/pnas.86.5.1434. PubMed: 2646633.
31. Fuller RS, Sterne RE, Thorner J, (1988) Enzymes required for yeast prohormone processing. Annu Rev Physiol 50: 345-362. doi:10.1146/annurev.ph.50.030188.002021. PubMed: 3288097.
32. Julius D, Brake A, Blair L, Kunisawa R, Thorner J, (1984) Isolation of the putative structural gene for the lysine-arginine-cleaving endopeptidase required for processing of yeast prepro-alpha-factor. Cell 37: 1075-1089. doi:10.1016/0092-8674(84)90442-2. PubMed: 6430565.
33. Rockwell NC, Thorner JW, (2004) The kindest cuts of all: crystal structures of Kex2 and furin reveal secrets of precursor processing. Trends Biochem Sci 29: 80-87. doi:10.1016/j.tibs.2003.12.006. PubMed: 15102434.
34. Rockwell NC, Krysan DJ, Komiyama T, Fuller RS, (2002) Precursor processing by kex2/furin proteases. Chem Rev 102: 4525-4548. doi:10.1021/cr010168i. PubMed: 12475200.
35. Bevan A, Brenner C, Fuller RS, (1998) Quantitative assessment of enzyme specificity in vivo: P2 recognition by Kex2 protease defined in a genetic system. Proc Natl Acad Sci U S A 95: 10384-10389. doi:10.1073/pnas.95.18.10384. PubMed: 9724712.
36. Rockwell NC, Wang GT, Krafft GA, Fuller RS, (1997) Internally consistent libraries of fluorogenic substrates demonstrate that Kex2 protease specificity is generated by multiple mechanisms. Biochemistry 36: 1912-1917. doi:10.1021/bi961779l. PubMed: 9048578.
37. Rockwell NC, Fuller RS, (1998) Interplay between S1 and S4 subsites in Kex2 protease: Kex2 exhibits dual specificity for the P4 side chain. Biochemistry 37: 3386-3391. doi:10.1021/bi972534r. PubMed: 9521659.
38. Rholam M, Brakch N, Germain D, Thomas DY, Fahy C, et al. (1995) Role of amino acid sequences flanking dibasic cleavage sites in precursor proteolytic processing. The importance of the first residue C-terminal of the cleavage site. Eur J Biochem 227: 707-714. doi:10.1111/j.1432-1033.1995.tb20192.x. PubMed: 7867629.
39. Germain D, Vernet T, Boileau G, Thomas DY, (1992) Expression of the Saccharomyces cerevisiae Kex2p endoprotease in inset cells. Evidence for a carboxy-terminal autoprocessing event. Eur J Biochem 204: 121-126. doi:10.1111/j.1432-1033.1992.tb16613.x. PubMed: 1740121.
40. Germain D, Dumas F, Vernet T, Bourbonnais Y, Thomas DY, et al. (1992) The pro-region of the Kex2 endoprotease of Saccharomyces cerevisiae is removed by self-processing. FEBS Lett 299: 283-286. doi:10.1016/0014-5793(92)80132-Z. PubMed: 1544507.
41. Kliman RM, Irving N, Santiago M, (2003) Selection conflicts, gene expression, and codon usage trends in yeast. J Mol Evol 57: 98-109. doi:10.1007/s00239-003-2459-9. PubMed: 12962310.
42. Barnard GC, Kull AR, Sharkey NS, Shaikh SS, Rittenhour AM, et al. (2010) High-throughput screening and selection of yeast cell lines expressing monoclonal antibodies. J Ind Microbiol Biotechnol 37: 961-971. doi:10.1007/s10295-010-0746-1. PubMed: 20711797.
43. Weis R, Luiten R, Skranc W, Schwab H, Wubbolts M, et al. (2004) Reliable high-throughput screening with Pichia pastoris by limiting yeast cell death phenomena. FEMS Yeast Res 5: 179-189. doi:10.1016/j.femsyr.2004.06.016. PubMed: 15489201.
44. Horvath A, Riezman H, (1994) Rapid protein extraction from Saccharomyces cerevisiae. Yeast 10: 1305-1310. doi:10.1002/yea.320101007. PubMed: 7900419.
45. Ogawa M, Matsuzaki Y, Nishikawa S, Hayashi S, Kunisada T, et al. (1991) Expression and function of c-kit in hemopoietic progenitor cells. J Exp Med 174: 63-71. doi:10.1084/jem.174.1.63. PubMed: 1711568.
46. Kent D, Copley M, Benz C, Dykstra B, Bowie M, et al. (2008) Regulation of hematopoietic stem cells by the steel factor/KIT signaling pathway. Clin Cancer Res 14: 1926-1930. doi:10.1158/1078-0432.CCR-07-5134. PubMed: 18381929.
47. Okayama Y, Kawakami T, (2006) Development, migration, and survival of mast cells. Immunol Res 34: 97-115. doi:10.1385/IR:34:2:97. PubMed: 16760571.
48. Rönnstrand L, (2004) Signal transduction via the stem cell factor receptor/c-Kit. Cell Mol Life Sci 61: 2535-2548. doi:10.1007/s00018-004-4189-6. PubMed: 15526160.
49. Wehrle-Haller B, (2003) The role of Kit-ligand in melanocyte development and epidermal homeostasis. Pigment Cell Res 16: 287-296. doi:10.1034/j.1600-0749.2003.00055.x. PubMed: 12753403.
50. Rossi P, Sette C, Dolci S, Geremia R, (2000) Role of c-kit in mammalian spermatogenesis. J Endocrinol Invest 23: 609-615. PubMed: 11079457.
51. Broudy VC, (1997) Stem cell factor and hematopoiesis. Blood 90: 1345-1364. PubMed: 9269751.
52. Mekori YA, Oh CK, Metcalfe DD, (1995) The role of c-Kit and its ligand, stem cell factor, in mast cell apoptosis. Int Arch Allergy Immunol 107: 136-138. doi:10.1159/000236955. PubMed: 7542059.
53. Avraham H, Vannier E, Cowley S, Jiang SX, Chi S, et al. (1992) Effects of the stem cell factor, c-kit ligand, on human megakaryocytic cells. Blood 79: 365-371. PubMed: 1370386.
54. Bader O, Krauke Y, Hube B, (2008) Processing of predicted substrates of fungal Kex2 proteinases from Candida albicans, C. glabrata, Saccharomyces cerevisiae and Pichia pastoris. BMC Microbiol 8: 116. doi:10.1186/1471-2180-8-116. PubMed: 18625069.