Comprehensive clone screening and evaluation of fed-batch strategies in a microbioreactor and lab scale stirred tank bioreactor system: Application on Pichia pastoris producing Rhizopus oryzae lipase

Microbial Cell Factories

Volumn 13, Issue 1, 2014, Pages

  Hemmerich, Johannes ^a   Adelantado, Núria ^b   Barrigón, José M ^b   Ponte, Xavier ^b   Hörmann, Astrid ^b,c   Ferrer, Pau ^b   Kensy, Frank ^a   Valero, Francisco ^b  

^a M2p labs GmbH   (Germany)

^b UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^c CENTRE FOR GENOMIC REGULATION CRG   (Spain)

Author keywords

Bioprocess development; Clone screening; Fed batch fermentation; Feeding strategies; Microbioreactor; Pichia pastoris; Rhizopus oryzae lipase; Scale up

Indexed keywords

ALCOHOL OXIDASE; GLUCOSE POLYMER; GLUCOSIDASE; GLYCEROL; METHANOL; RNA DIRECTED DNA POLYMERASE;

ARTICLE; CLONAL VARIATION; CONTROLLED STUDY; ENZYME ACTIVITY; FED BATCH FERMENTATION; FUNGAL STRAIN; FUNGUS GROWTH; GLUCOSE INTAKE; LIPOLYSIS; MICROBIOLOGICAL EXAMINATION; MICROBIOREACTOR SYSTEM; MOLECULAR CLONING; NONHUMAN; OPTICAL DENSITY; OXIDATION; OXYGEN CONSUMPTION; PICHIA ANGUSTA; PICHIA PASTORIS; RHIZOPUS ORYZAE; STIRRED REACTOR; UNFOLDED PROTEIN RESPONSE;

PICHIA PASTORIS; RHIZOPUS ORYZAE;

BATCH CELL CULTURE TECHNIQUES; BIOMASS; BIOREACTORS; FUNGAL PROTEINS; GENETIC VECTORS; GLYCEROL; LIPASE; METHANOL; PICHIA; RECOMBINANT PROTEINS; RHIZOPUS;

EID: 84899486694     PISSN: None     EISSN: 14752859     Source Type: Journal    
DOI: 10.1186/1475-2859-13-36     Document Type: Article

References (58)

1. Corchero JL, Gasser B, Resina D, Smith W, Parrilli E, Vázquez F, Abasolo I, Giuliani M, Jäntti J, Ferrer P, Saloheimo M, Mattanovich D, Schwartz S, Tutino ML, Villaverde A. Unconventional microbial systems for the cost-efficient production of high-quality protein therapeutics. Biotechnol Adv 2013, 31:140-153. 10.1016/j.biotechadv.2012.09.001, 22985698.
2. Gasser B, Prielhofer R, Marx H, Maurer M, Nocon J, Steiger M, Puxbaum V, Sauer M, Mattanovich D. Pichia pastoris: protein production host and model organism for biomedical research. Future Microbiol 2013, 8:191-208. 10.2217/fmb.12.133, 23374125.
3. Potvin G, Ahmad A, Zhang Z. Bioprocess engineering aspects of heterologous protein production in Pichia pastoris: a review. Biochem Eng J 2012, 64:91-105.
4. Cereghino JL, Cregg JM. Heterologous protein expression in the methylotrophic yeast Pichia pastoris. FEMS Microbiol Rev 2000, 24:45-66. 10.1111/j.1574-6976.2000.tb00532.x, 10640598.
5. Cregg JM, Cereghino JL, Shi J, Higgins DR. Recombinant protein expression in Pichia pastoris. Mol Biotechnol 2000, 16:23-52. 10.1385/MB:16:1:23, 11098467.
6. Cos O, Ramón R, Montesinos J, Valero F. Operational strategies, monitoring and control of heterologous protein production in the methylotrophic yeast Pichia pastoris under different promotors: a review. Microb Cell Fact 2006, 5:17. 10.1186/1475-2859-5-17, 1564409, 16600031.
7. Arnau C, Ramon R, Casas C, Valero F. Optimization of the heterologous production of a Rhizopus oryzae lipase in Pichia pastoris system using mixed substrates on controlled fed-batch bioprocess. Enzyme Microb Tech 2010, 46:494-500.
8. Jungo C, Schenk J, Pasquier M, Marison IW, von SU. A quantitative analysis of the benefits of mixed feeds of sorbitol and methanol for the production of recombinant avidin with Pichia pastoris. J Biotechnol 2007, 131:57-66. 10.1016/j.jbiotec.2007.05.019, 17614154.
9. Files D, Ogawa M, Scaman CH, Baldwin SA. A Pichia pastoris fermentation process for producing high-levels of recombinant human cystatin-C. Enzyme Microb Tech 2001, 29:335-340.
10. Brooks CL, Morrison M, Joanne Lemieux M. Rapid expression screening of eukaryotic membrane proteins in Pichia pastoris. Protein Sci 2013, 22:425-433. 10.1002/pro.2223, 23339074.
11. Lundholt BK, Scudder KM, Pagliaro L. A simple technique for reducing edge effect in cell-based assays. J Biomol Screen 2003, 8:566-570. 10.1177/1087057103256465, 14567784.
12. Rohe P, Venkanna D, Kleine B, Freudl R, Oldiges M. An automated workflow for enhancing microbial bioprocess optimization on a novel microbioreactor platform. Microb Cell Fact 2012, 11:144. 10.1186/1475-2859-11-144, 3526558, 23113930.
13. Puskeiler R, Kaufmann K, Weuster-Botz D. Development, parallelization, and automation of a gas-inducing milliliter-scale bioreactor for high-throughput bioprocess design (HTBD). Biotechnol Bioeng 2005, 89:512-523. 10.1002/bit.20352, 15669089.
14. Funke M, Buchenauer A, Mokwa W, Kluge S, Hein L, Müller C, Kensy F, Büchs J. Bioprocess control in microscale: scalable fermentations in disposable and user-friendly microfluidic systems. Microb Cell Fact 2010, 9:86. 10.1186/1475-2859-9-86, 3000389, 21073740.
15. Moucha T, Linek V, Prokopova E. Gas hold-up, mixing time and gas-liquid volumetric mass transfer coefficient of various multiple-impeller configurations. Rushton turbine, pitched blade and techmix impeller and their combinations. Chem Eng Sci 2003, 58:1839-1846.
16. Lübbert A. Advanced methods for bioreactor characterization. J Biotechnol 1992, 25:145-182. 10.1016/0168-1656(92)90113-N, 1368459.
17. van't Riet K. Review of measuring methods and results in nonviscous gas-liquid mass transfer in stirred vessels. Ind Eng Chem Proc Des Dev 1979, 18:357-364.
18. Funke M, Diederichs S, Kensy F, Müller C, Büchs J. The baffled microtiter plate: increased oxygen transfer and improved online monitoring in small scale fermentations. Biotechnol Bioeng 2009, 103:1118-1128. 10.1002/bit.22341, 19449392.
19. Isett K, George H, Herber W, Amanullah A. Twenty-four-well plate miniature bioreactor high-throughput system: assessment for microbial cultivations. Biotechnol Bioeng 2007, 98:1017-1028. 10.1002/bit.21484, 17486656.
20. Kensy F, Zang E, Faulhammer C, Tan R, Büchs J. Validation of a high-throughput fermentation system based on online monitoring of biomass and fluorescence in continuously shaken microtiter plates. Microb Cell Fact 2009, 8:31. 10.1186/1475-2859-8-31, 2700080, 19497126.
21. Huber R, Ritter D, Hering T, Hillmer A, Kensy F, Müller C, Wang L, Büchs J. Robo-Lector - A novel platform for automated high-throughput cultivations in microtiter plates with high information content. Microb Cell Fact 2009, 8:42. 10.1186/1475-2859-8-42, 2731075, 19646274.
22. Baumann K, Adelantado N, Lang C, Mattanovich D, Ferrer P. Protein trafficking, ergosterol biosynthesis and membrane physics impact recombinant protein secretion in Pichia pastoris. Microb Cell Fact 2011, 10:93. 10.1186/1475-2859-10-93, 3219557, 22050768.
23. Boettner M, Steffens C, von MC, Bork P, Stahl U, Lang C. Sequence-based factors influencing the expression of heterologous genes in the yeast Pichia pastoris - A comparative view on 79 human genes. J Biotechnol 2007, 130:1-10. 10.1016/j.jbiotec.2007.02.019, 17389146.
24. Holmes WJ, Darby RAJ, Wilks MDB, Smith R, Bill RM. Developing a scalable model of recombinant protein yield from Pichia pastoris: the influence of culture conditions, biomass and induction regime. Microb Cell Fact 2009, 8:35. 10.1186/1475-2859-8-35, 2717918, 19570229.
25. Curvers S, Brixius P, Klauser T, Thömmes J, Weuster-Botz D, Takors R, Wandrey C. Human Chymotrypsinogen B production with Pichia pastoris by integrated development of fermentation and downstream processing. Part 1. Fermentation. Biotechnol Prog 2001, 17:495-502. 10.1021/bp000164j, 11386871.
26. Anderlei T, Zang W, Papaspyrou M, Büchs J. Online respiration activity measurement (OTR, CTR, RQ) in shake flasks. Biochem Eng J 2004, 17:187-194.
27. Anderlei T, Büchs J. Device for sterile online measurement of the oxygen transfer rate in shaking flasks. Biochem Eng J 2000, 3478:1-6.
28. Qin X, Qian J, Yao G, Zhuang Y, Zhang S, Chu J. GAP promoter library for fine-tuning of gene expression in Pichia pastoris. Appl Environ Microbiol 2011, 77:3600-3608. 10.1128/AEM.02843-10, 3127614, 21498769.
29. Hartner FS, Ruth C, Langenegger D, Johnson SN, Hyka P, Lin-Cereghino GP, Lin-Cereghino J, Kovar K, Cregg JM, Glieder A. Promoter library designed for fine-tuned gene expression in Pichia pastoris. Nucleic Acids Res 2008, 36:e76. 10.1093/nar/gkn369, 2475614, 18539608.
30. Sandström AG, Engström K, Nyhlen J, Kasrayan A, Bäckvall J. Directed evolution of Candida antarctica lipase A using an episomaly replicating yeast plasmid. Protein Eng Des Sel 2009, 22:413-420. 10.1093/protein/gzp019, 19509064.
31. Murasugi A, Tohma-Aiba Y. Comparison of three signals for secretory expression of recombinant human midkine in Pichia pastoris. Biosci Biotechnol Biochem 2001, 65:2291-2293. 10.1271/bbb.65.2291, 11758924.
32. Legmann R, Benoit B, Fedechko RW, Deppeler CL, Srinivasan S, Robins RH, McCormick EL, Ferrick DA, Rodgers ST, Russo AP. A strategy for clone selection under different production conditions. Biotechnol Prog 2011, 27:757-765. 10.1002/btpr.577, 21448991.
33. Minning S, Serrano A, Ferrer P, Solá C, Schmid RD, Valero F. Optimization of the high-level production of Rhizopus oryzae lipase in Pichia pastoris. J Biotechnol 2001, 86:59-70. 10.1016/S0168-1656(00)00402-8, 11223145.
34. Invitrogen Pichia fermentation process guidelines version B 05/03/02. Available online: http://tools.lifetechnologies.com/content/sfs/manuals/pichiaferm_prot.pdf, last accessed 25/05/2013, Invitrogen.
35. Resina D, Maurer M, Cos O, Arnau C, Carnicer M, Marx H, Gasser B, Valero F, Mattanovich D, Ferrer P. Engineering of bottlenecks in Rhizopus oryzae lipase production in Pichia pastoris using the nitrogen source-regulated FLD1 promoter. N Biotechnol 2009, 25:396-403. 10.1016/j.nbt.2009.01.008, 19552885.
36. Kim S. Optimization of the functional expression of Coprinus cinereus peroxidase in Pichia pastoris by varying the host and promoter. J Microbiol Biotechnol 2009, 19:966-971. 10.4014/jmb.0901.018, 19809254.
37. Lee CC, Williams TG, Wong DW, Robertson GH. An episomal expression vector for screening mutant gene libraries in Pichia pastoris. Plasmid 2005, 54:80-85. 10.1016/j.plasmid.2004.12.001, 15907541.
38. Mack M, Wannemacher M, Hobl B, Pietschmann P, Hock B. Comparison of two expression platforms in respect to protein yield and quality: Pichia pastoris versus Pichia angusta. Protein Express Purif 2009, 66:165-171.
39. Hellwig S, Emde F, Raven NPG, Henke M, van der Logt P, Fischer R. Analysis of single-chain antibody production in Pichia pastoris using on-line methanol control in fed-batch and mixed-feed fermentations. Biotechnol Bioeng 2001, 74:344-352. 10.1002/bit.1125, 11410859.
40. Hellwig S, Robin F, Drossard J, Raven NPG, Vaquero-Martin C, Shively JE, Fischer R. Production of carcinoembryonic antigen (CEA) N-A3 domain in Pichia pastoris by fermentation. Biotechnol Appl Biochem 1999, 30(Pt 3):267-275.
41. Resina D, Bollók M, Khatri NK, Valero F, Neubauer P, Ferrer P. Transcriptional response of P. pastoris in fed-batch cultivations to Rhizopus oryzae lipase production reveals UPR induction. Microb Cell Fact 2007, 6:21. 10.1186/1475-2859-6-21, 1950523, 17634115.
42. Jordà J, Jouhten P, Cámara E, Maaheimo H, Albiol J, Ferrer P. Metabolic flux profiling of recombinant protein secreting Pichia pastoris growing on glucose:methanol mixtures. Microb Cell Fact 2012, 11:57. 10.1186/1475-2859-11-57, 3443025, 22569166.
43. Cámara E, Jordà J, Jouhten P, Maaheimo H, Albiol J, Ferrer P. Impact of recombinant protein production on the energy metabolism of Pichia pastoris growing on glucose:methanol mixtures. [Abstract]. 2012, Belgirate, Italy: 2nd Conference on Microbial Stress: from molecules to systems.
44. Viader-Salvadó JM, Cab-Barrera EL, Galán-Wong LJ, Guerrero-Olazarán M. Genotyping of recombinant Pichia pastoris strains. Cell Mol Biol Lett 2006, 11:348-359. 10.2478/s11658-006-0029-z, 16847557.
45. Mayer AF, Hellmuth K, Schlieker H, Lopez-Ulibarri R, Oertel S, Dahlems U, Strasser AW, van Loon AP. An expression system matures: a highly efficient and cost-effective process for phytase production by recombinant strains of Hansenula polymorpha. Biotechnol Bioeng 1999, 63:373-381. 10.1002/(SICI)1097-0290(19990505)63:3<373::AID-BIT14>3.0.CO;2-T, 10099617.
46. Green H, Rheinwald JG. Method of controllably releasing glucose to a cell culture medium. US 3,926,723 1975,
47. Surribas A, Resina D, Ferrer P, Valero F. Rivoflavin may interfere with on-line monitoring of secreted green fluorescence protein fusion proteins in Pichia pastoris. Microb Cell Fact 2007, 6:15. 10.1186/1475-2859-6-15, 1884171, 17511861.
48. Berdichevsky M, d'Anjou M, Mallem MR, Shaikh SS, Potgieter TI. Improved production of monoclonal antibodies through oxygen-limited cultivation of glycoengineered yeast. J Biotechnol 2011, 155:217-224. 10.1016/j.jbiotec.2011.06.021, 21723345.
49. Arnau C, Casas C, Valero F. The effect of glycerol mixed substrate on the heterologous production of a Rhizopus oryzae lipase in Pichia pastoris system. Biochem Eng J 2011, 57:30-37.
50. Scheidle M, Jeude M, Dittrich B, Denter S, Kensy F, Suckow M, Klee D, Büchs J. High-throughput screening of Hansenula polymorpha clones in the batch compared with the controlled-release fed-batch mode on a small scale. FEMS Yeast Res 2010, 10:83-92. 10.1111/j.1567-1364.2009.00586.x, 19849718.
51. Hermann R, Walther N, Maier U, Büchs J. Optical method for the determination of the oxygen-transfer capacity of small bioreactors based on sulfite oxidation. Biotechnol Bioeng 2001, 74:355-363. 10.1002/bit.1126, 11427937.
52. Hang H, Ye X, Guo M, Chu J, Zhuang Y, Zhang M, Zhang S. A simple fermentation strategy for high-level production of recombinant phytase by Pichia pastoris using glucose as the growth substrate. Enzy Microb Technol 2009, 44:185-188.
53. Paulová L, Hyka P, Branská B, Melzoch K, Kovar K. Use of a mixture of glucose and methanol as substrates for the production of recombinant trypsinogen in continuous cultures with Pichia pastoris Mut+. J Biotechnol 2012, 157:180-188. 10.1016/j.jbiotec.2011.10.010, 22123532.
54. Kim S, Warburton S, Boldogh I, Svensson C, Pon L, d'Anjou M, Stadheim TA, Choi B. Regulation of alcohol oxidase 1 (AOX1) promoter and peroxisome biogenesis in different fermentation processes in Pichia pastoris. J Biotechnol 2013, 166:174-181. 10.1016/j.jbiotec.2013.05.009, 23735484.
55. Baumann K, Carnicer M, Dragosits M, Graf AB, Stadlmann J, Jouhten P, Maaheimo H, Gasser B, Albiol J, Mattanovich D, Ferrer P. A multi-level study of recombinant Pichia pastoris in different oxygen conditions. BMC Syst Biol 2010, 4:141. 10.1186/1752-0509-4-141, 2987880, 20969759.
56. Ruottinen M, Bollok M, Kogler M, Neubauer A, Krause M, Hamalainen E, Myllyharju J, Vasala A, Neubauer P. Improved production of human type II procollagen in the yeast Pichia pastoris in shake flasks by a wireless-controlled fed-batch system. BMC Biotechnol 2008, 8:33. 10.1186/1472-6750-8-33, 2315644, 18371201.
57. Guerfal M, Ryckaert S, Jacobs PP, Ameloot P, van Craenenbroeck K, Derycke R, Callewaert N. The HAC1 gene from Pichia pastoris: characterization and effect of its overexpression on the production of secreted, surface displayed and membrane proteins. Microb Cell Fact 2010, 9:49. 10.1186/1475-2859-9-49, 2905327, 20591165.
58. Lin-Cereghino J, Wong WW, Xiong S, Giang W, Luong LT, Vu J, Johnson SD, Lin-Cereghino GP. Condensed protocol for competent cell preparation and transformation of the methylotrophic yeast Pichia pastoris. Biotechniques 2005, 38:44-48. 10.2144/05381BM04, 2504082, 15679083.