Methanol‐Free Protein Expression in Komagataella phaffii With Magnetic or Non‐Magnetic Heating

ABSTRACT Komagataella phaffii is among the most widely used expression systems, with methanol‐inducible promoters being preferred for protein expression due to their stringent regulation and exceptional strength. However, the applicability of this system, particularly in food and pharmaceutical prod...

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Main Authors: Ibrahim Dagci, Seyda Yildiz Arslan, Kubra Solak, Melek Acar, Yagmur Unver, Ahmet Mavi
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Microbial Biotechnology
Subjects:
Online Access:https://doi.org/10.1111/1751-7915.70183
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author Ibrahim Dagci
Seyda Yildiz Arslan
Kubra Solak
Melek Acar
Yagmur Unver
Ahmet Mavi
author_facet Ibrahim Dagci
Seyda Yildiz Arslan
Kubra Solak
Melek Acar
Yagmur Unver
Ahmet Mavi
author_sort Ibrahim Dagci
collection DOAJ
description ABSTRACT Komagataella phaffii is among the most widely used expression systems, with methanol‐inducible promoters being preferred for protein expression due to their stringent regulation and exceptional strength. However, the applicability of this system, particularly in food and pharmaceutical products, is limited by methanol's toxic and pro‐inflammatory properties. Therefore, obtaining a novel methanol‐free expression system is necessary. In this study, we obtained a novel expression plasmid, pHSPαA, carrying the HSP70 promoter (PHSP70) to regulate heterologous expression through heat induction. The extracellular expression of azurin was achieved using this methanol‐free system under the control of PHSP70, induced by either magnetic or non‐magnetic heating. To enhance heat‐induced expression, recombinant cells were immobilised with Fe3O4@PEI25 kDa nanoparticles, which facilitated heat release under an AC magnetic field, thereby increasing cell permeability and protein secretion. A time‐dependent increase in protein expression was observed in non‐magnetic heating but not under magnetic heating. However, immobilised cells exhibited a higher protein secretion capacity compared to non‐immobilised cells. These findings suggest that the novel methanol‐free expression system represents a promising alternative for heterologous gene expression, particularly for the production of therapeutically relevant and food‐grade recombinant proteins.
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series Microbial Biotechnology
spelling doaj-art-e5eba15ea49c4817a8b861e35377f8d12025-08-20T03:24:02ZengWileyMicrobial Biotechnology1751-79152025-06-01186n/an/a10.1111/1751-7915.70183Methanol‐Free Protein Expression in Komagataella phaffii With Magnetic or Non‐Magnetic HeatingIbrahim Dagci0Seyda Yildiz Arslan1Kubra Solak2Melek Acar3Yagmur Unver4Ahmet Mavi5Department of Molecular Biology and Genetics Institute of Science and Technology, Atatürk University Erzurum TürkiyeDepartment of Molecular Biology and Genetics Institute of Science and Technology, Atatürk University Erzurum TürkiyeDepartment of Molecular Biology and Genetics Faculty of Science, Atatürk University Erzurum TürkiyeDepartment of Molecular Biology and Genetics Institute of Science and Technology, Atatürk University Erzurum TürkiyeDepartment of Molecular Biology and Genetics Faculty of Science, Atatürk University Erzurum TürkiyeEast Anatolia High Technology Application and Research Center (DAYTAM) Atatürk University Erzurum TürkiyeABSTRACT Komagataella phaffii is among the most widely used expression systems, with methanol‐inducible promoters being preferred for protein expression due to their stringent regulation and exceptional strength. However, the applicability of this system, particularly in food and pharmaceutical products, is limited by methanol's toxic and pro‐inflammatory properties. Therefore, obtaining a novel methanol‐free expression system is necessary. In this study, we obtained a novel expression plasmid, pHSPαA, carrying the HSP70 promoter (PHSP70) to regulate heterologous expression through heat induction. The extracellular expression of azurin was achieved using this methanol‐free system under the control of PHSP70, induced by either magnetic or non‐magnetic heating. To enhance heat‐induced expression, recombinant cells were immobilised with Fe3O4@PEI25 kDa nanoparticles, which facilitated heat release under an AC magnetic field, thereby increasing cell permeability and protein secretion. A time‐dependent increase in protein expression was observed in non‐magnetic heating but not under magnetic heating. However, immobilised cells exhibited a higher protein secretion capacity compared to non‐immobilised cells. These findings suggest that the novel methanol‐free expression system represents a promising alternative for heterologous gene expression, particularly for the production of therapeutically relevant and food‐grade recombinant proteins.https://doi.org/10.1111/1751-7915.70183alternating magnetic fieldHSP70 promoterKomagataella phaffiimagnetic nanoparticlesmethanol‐free expression
spellingShingle Ibrahim Dagci
Seyda Yildiz Arslan
Kubra Solak
Melek Acar
Yagmur Unver
Ahmet Mavi
Methanol‐Free Protein Expression in Komagataella phaffii With Magnetic or Non‐Magnetic Heating
Microbial Biotechnology
alternating magnetic field
HSP70 promoter
Komagataella phaffii
magnetic nanoparticles
methanol‐free expression
title Methanol‐Free Protein Expression in Komagataella phaffii With Magnetic or Non‐Magnetic Heating
title_full Methanol‐Free Protein Expression in Komagataella phaffii With Magnetic or Non‐Magnetic Heating
title_fullStr Methanol‐Free Protein Expression in Komagataella phaffii With Magnetic or Non‐Magnetic Heating
title_full_unstemmed Methanol‐Free Protein Expression in Komagataella phaffii With Magnetic or Non‐Magnetic Heating
title_short Methanol‐Free Protein Expression in Komagataella phaffii With Magnetic or Non‐Magnetic Heating
title_sort methanol free protein expression in komagataella phaffii with magnetic or non magnetic heating
topic alternating magnetic field
HSP70 promoter
Komagataella phaffii
magnetic nanoparticles
methanol‐free expression
url https://doi.org/10.1111/1751-7915.70183
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