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Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-21535
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dc.contributor.authorBorčinová, Martina-
dc.contributor.authorRaschmanová, Hana-
dc.contributor.authorZamora, Iwo-
dc.contributor.authorLooser, Verena-
dc.contributor.authorMarešová, Helena-
dc.contributor.authorHirsch, Sven-
dc.contributor.authorKyslík, Pavel-
dc.contributor.authorKovar, Karin-
dc.date.accessioned2021-02-04T10:35:10Z-
dc.date.available2021-02-04T10:35:10Z-
dc.date.issued2020-
dc.identifier.issn0175-7598de_CH
dc.identifier.issn1432-0614de_CH
dc.identifier.urihttps://digitalcollection.zhaw.ch/handle/11475/21535-
dc.descriptionErworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)de_CH
dc.description.abstractTo take full advantage of recombinant Pichia pastoris (Komagataella phaffii) as a production system for heterologous proteins, the complex protein secretory process should be understood and optimised by circumventing bottlenecks. Typically, little or no attention has been paid to the fate of newly synthesised protein inside the cell, or its passage through the secretory pathway, and only the secreted product is measured. However, the system's productivity (i.e. specific production rate qp), includes productivity of secreted (qp,extra) plus intracellularly accumulated (qp,intra) protein. In bioreactor cultivations with P. pastoris producing penicillin G acylase, we studied the dynamics of product formation, i.e. both the specific product secretion (qp,extra) and product retention (qp,intra) as functions of time, as well as the kinetics, i.e. productivity in relation to specific growth rate (μ). Within the time course, we distinguished (I) an initial phase with constant productivities, where the majority of product accumulated inside the cells, and qp,extra, which depended on μ in a bell-shaped manner; (II) a transition phase, in which intracellular product accumulation reached a maximum and productivities (intracellular, extracellular, overall) were changing; (III) a new phase with constant productivities, where secretion prevailed over intracellular accumulation, qp,extra was linearly related to μ and was up to three times higher than in initial phase (I), while qp,intra decreased 4-6-fold. We show that stress caused by heterologous protein production induces cellular imbalance leading to a secretory bottleneck that ultimately reaches equilibrium. This understanding may help to develop cultivation strategies for improving protein secretion from P. pastoris.de_CH
dc.language.isoende_CH
dc.publisherSpringerde_CH
dc.relation.ispartofApplied Microbiology and Biotechnologyde_CH
dc.rightshttp://creativecommons.org/licenses/by/4.0/de_CH
dc.subjectPichia pastorisde_CH
dc.subjectPenicillin G acylasede_CH
dc.subjectSpecific rate of product formationde_CH
dc.subjectProcess optimisationde_CH
dc.subjectSecretion of a heterologous proteinde_CH
dc.subjectFedbatch bioreactor cultivationde_CH
dc.subject.ddc660.6: Biotechnologiede_CH
dc.titleProduction and secretion dynamics of prokaryotic Penicillin G acylase in Pichia pastorisde_CH
dc.typeBeitrag in wissenschaftlicher Zeitschriftde_CH
dcterms.typeTextde_CH
zhaw.departementLife Sciences und Facility Managementde_CH
zhaw.organisationalunitInstitut für Computational Life Sciences (ICLS)de_CH
zhaw.organisationalunitInstitut für Chemie und Biotechnologie (ICBT)de_CH
dc.identifier.doi10.1007/s00253-020-10669-xde_CH
dc.identifier.doi10.21256/zhaw-21535-
dc.identifier.pmid32424437de_CH
zhaw.funding.euNode_CH
zhaw.issue13de_CH
zhaw.originated.zhawYesde_CH
zhaw.pages.end5800de_CH
zhaw.pages.start5787de_CH
zhaw.publication.statuspublishedVersionde_CH
zhaw.volume104de_CH
zhaw.publication.reviewPeer review (Publikation)de_CH
zhaw.webfeedBiomedical Simulationde_CH
zhaw.author.additionalNode_CH
zhaw.display.portraitYesde_CH
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Borčinová, M., Raschmanová, H., Zamora, I., Looser, V., Marešová, H., Hirsch, S., Kyslík, P., & Kovar, K. (2020). Production and secretion dynamics of prokaryotic Penicillin G acylase in Pichia pastoris. Applied Microbiology and Biotechnology, 104(13), 5787–5800. https://doi.org/10.1007/s00253-020-10669-x
Borčinová, M. et al. (2020) ‘Production and secretion dynamics of prokaryotic Penicillin G acylase in Pichia pastoris’, Applied Microbiology and Biotechnology, 104(13), pp. 5787–5800. Available at: https://doi.org/10.1007/s00253-020-10669-x.
M. Borčinová et al., “Production and secretion dynamics of prokaryotic Penicillin G acylase in Pichia pastoris,” Applied Microbiology and Biotechnology, vol. 104, no. 13, pp. 5787–5800, 2020, doi: 10.1007/s00253-020-10669-x.
BORČINOVÁ, Martina, Hana RASCHMANOVÁ, Iwo ZAMORA, Verena LOOSER, Helena MAREŠOVÁ, Sven HIRSCH, Pavel KYSLÍK und Karin KOVAR, 2020. Production and secretion dynamics of prokaryotic Penicillin G acylase in Pichia pastoris. Applied Microbiology and Biotechnology. 2020. Bd. 104, Nr. 13, S. 5787–5800. DOI 10.1007/s00253-020-10669-x
Borčinová, Martina, Hana Raschmanová, Iwo Zamora, Verena Looser, Helena Marešová, Sven Hirsch, Pavel Kyslík, and Karin Kovar. 2020. “Production and Secretion Dynamics of Prokaryotic Penicillin G Acylase in Pichia Pastoris.” Applied Microbiology and Biotechnology 104 (13): 5787–5800. https://doi.org/10.1007/s00253-020-10669-x.
Borčinová, Martina, et al. “Production and Secretion Dynamics of Prokaryotic Penicillin G Acylase in Pichia Pastoris.” Applied Microbiology and Biotechnology, vol. 104, no. 13, 2020, pp. 5787–800, https://doi.org/10.1007/s00253-020-10669-x.


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