Engineered Folding and Secretion for Expression Improvement of α‐Amylase in Komagataella Phaffii

ABSTRACT α‐Amylase is the second most widely produced enzyme globally, with diverse applications in the fields of food, pharmaceutical, bioenergy, papermaking, etc. However, natural α‐amylase often fails to withstand the extreme conditions encountered in industrial processes, such as low pH and high...

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Main Authors: Yilun Zhang, Xingbin Wang, Bei Han, Chaoying Yao, Qi Liu, Menghao Cai
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Food Bioengineering
Subjects:
Online Access:https://doi.org/10.1002/fbe2.70005
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author Yilun Zhang
Xingbin Wang
Bei Han
Chaoying Yao
Qi Liu
Menghao Cai
author_facet Yilun Zhang
Xingbin Wang
Bei Han
Chaoying Yao
Qi Liu
Menghao Cai
author_sort Yilun Zhang
collection DOAJ
description ABSTRACT α‐Amylase is the second most widely produced enzyme globally, with diverse applications in the fields of food, pharmaceutical, bioenergy, papermaking, etc. However, natural α‐amylase often fails to withstand the extreme conditions encountered in industrial processes, such as low pH and high temperatures. Previous studies identified an α‐amylase derived from deep‐sea sources with resistance to low pH, and subsequent amino acid mutations well enhanced its thermal stability. Nevertheless, the advantageous enzyme mutant exhibited low expression levels in Escherichia coli, highlighting the need for a more suitable expression host. In this study, an engineered industrial host, Komagataella phaffii, was involved for heterologous production of α‐amylase. High‐efficiency signal peptides were screened and multi‐copy integrant strains were constructed to achieve a high‐yield strain. A total of 31 key chaperones and 11 vesicle transport factors were further investigated to facilitate protein folding and secretion, which resulted in a 3.4‐fold increase in α‐amylase production. Finally, batch fermentation in a 3‐L bioreactor achieved a maximum α‐amylase activity of 2.5 × 104 U/mL. This study demonstrates the development of a high‐yield α‐amylase strain for potential industrial applications, offering valuable insights and strategies for engineering high‐producing strains of other industrial enzymes.
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issn 2770-2081
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series Food Bioengineering
spelling doaj-art-a47eef71803543fa8aeddd78393448a82025-08-20T02:27:20ZengWileyFood Bioengineering2770-20812025-03-014131410.1002/fbe2.70005Engineered Folding and Secretion for Expression Improvement of α‐Amylase in Komagataella PhaffiiYilun Zhang0Xingbin Wang1Bei Han2Chaoying Yao3Qi Liu4Menghao Cai5State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology Shanghai ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology Shanghai ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology Shanghai ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology Shanghai ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology Shanghai ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology Shanghai ChinaABSTRACT α‐Amylase is the second most widely produced enzyme globally, with diverse applications in the fields of food, pharmaceutical, bioenergy, papermaking, etc. However, natural α‐amylase often fails to withstand the extreme conditions encountered in industrial processes, such as low pH and high temperatures. Previous studies identified an α‐amylase derived from deep‐sea sources with resistance to low pH, and subsequent amino acid mutations well enhanced its thermal stability. Nevertheless, the advantageous enzyme mutant exhibited low expression levels in Escherichia coli, highlighting the need for a more suitable expression host. In this study, an engineered industrial host, Komagataella phaffii, was involved for heterologous production of α‐amylase. High‐efficiency signal peptides were screened and multi‐copy integrant strains were constructed to achieve a high‐yield strain. A total of 31 key chaperones and 11 vesicle transport factors were further investigated to facilitate protein folding and secretion, which resulted in a 3.4‐fold increase in α‐amylase production. Finally, batch fermentation in a 3‐L bioreactor achieved a maximum α‐amylase activity of 2.5 × 104 U/mL. This study demonstrates the development of a high‐yield α‐amylase strain for potential industrial applications, offering valuable insights and strategies for engineering high‐producing strains of other industrial enzymes.https://doi.org/10.1002/fbe2.70005K. phaffiimolecular chaperonemulticopyvesicle transport factorα‐amylase
spellingShingle Yilun Zhang
Xingbin Wang
Bei Han
Chaoying Yao
Qi Liu
Menghao Cai
Engineered Folding and Secretion for Expression Improvement of α‐Amylase in Komagataella Phaffii
Food Bioengineering
K. phaffii
molecular chaperone
multicopy
vesicle transport factor
α‐amylase
title Engineered Folding and Secretion for Expression Improvement of α‐Amylase in Komagataella Phaffii
title_full Engineered Folding and Secretion for Expression Improvement of α‐Amylase in Komagataella Phaffii
title_fullStr Engineered Folding and Secretion for Expression Improvement of α‐Amylase in Komagataella Phaffii
title_full_unstemmed Engineered Folding and Secretion for Expression Improvement of α‐Amylase in Komagataella Phaffii
title_short Engineered Folding and Secretion for Expression Improvement of α‐Amylase in Komagataella Phaffii
title_sort engineered folding and secretion for expression improvement of α amylase in komagataella phaffii
topic K. phaffii
molecular chaperone
multicopy
vesicle transport factor
α‐amylase
url https://doi.org/10.1002/fbe2.70005
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